Sentinel node biopsy can decrease the morbidity of breast cancer treatment significantly by sparing many patients of axillary lymph node dissection and resulting arm lymphedema. Despite widespread use of sentinel node mapping for breast cancer patients almost all aspects of this procedure are controversial; such as: type of the radiotracer, eligibility, time of injection, etc. One of these controversial issues is the efficacy of 2 days protocol (injection of the tracer on one day and sentinel node mapping and surgery on the following day). The main reason to perform 2 days protocol is the ease of operation room scheduling the patient does not need to complete injection and imaging in the nuclear medicine department. Despite widespread use of 2 days protocol for sentinel node mapping, very few studies have specifically evaluated this protocol in comparison to 1 day protocol and also the false negative rate which is the better index of sentinel node mapping success. Most of the above studies used tracers with large particle size such as (99m)Tc-sulfur colloid. Tracers with small particle size can theoretically be washed out from the real sentinel nodes and move to the second echelon nodes, so some recommended using large particle size radiotracers for the 2 days protocol. In this study, we compared the false negative rate of sentinel node mapping between 1 and 2 days protocols using intradermal injection of (99m)Tc-antimony sulfide colloid ((99m)Tc-SbSC) which has very small particle size. Eighty patients with early stage breast cancer (clinical stages of I and II) were evaluated. The diagnosis of the breast cancer was established by either excisional or core needle biopsy. The patients didn't take any chemotherapeutic drug before surgery and were divided into two groups: 1 day (Group I) and 2 days (Group II) protocols (45 in Group I and 35 in Group II). For Group I, periareolar intradermal injections of 0.5Bq/0.2mL (99m)Tc-SbSC were applied for patients without previous excisional biopsy. For patients with excisional biopsy two intradermal injections of 0.5Bq/0.2mL (99m)Tc-SbSC were used on both sides of the incision line. All injections were followed by gentle massage for 1min. For Group II, the same injection techniques were used but the dose of the tracer was doubled. Anterior, and lateral spot views were acquired 30min after the injection (5min/image, 128Χ128 matrix) using a dual head gamma camera (E.CAM Siemens) and parallel hole low energy high resolution collimator. The operation was performed 4h (for Group I) or 20h (for Group II) post radiotracer injection. All patients received 2mL patent blue V dye in a subdermal and periareolar fashion, 2min after general anesthesia. A surgical gamma probe (EUROPROBE, France) was used for harvesting the sentinel lymph nodes during surgery. As sentinel node was defined any blue node or any node with an ex vivo radioisotope count of twofold or greater than the axillary background. After completion of sentinel node biopsy, all patients underwent standard axillary lymph node dissection. The study was approved by our local ethical committee and all patients gave their informed consent before inclusion into the study. Quantitative data were expressed as mean±SD. For comparison between groups, independent sample student's t-test for quantitative variables, and chi-square or Fisher's exact tests for categorical variables were used. P-values less than 0.05 were considered statistically significant. SPSS version 11.5 was used for statistical analyses. The patients characteristics are shown in Table I. These general characteristics were not significantly different between the study groups (P>0.05). Detection rate was 100% for both Groups. The median number of sentinel nodes in both Groups was one sentinel node. The mean number of detected sentinel nodes during surgery was not statistically different between groups (1.28±0.7 and 1.32±0.6 for Group I and II respectively). One false negative sentinel node case with positive axillary nodes after dissection was found in both groups. This amounts to 6.25% and 6.66% false negative rate for Group I and II patients respectively. During surgery mean count rate at the injection site was 243123±22134 and 29430±2125 for Groups I and II, respectively. Mean count rate at the sentinel nodes was 4345±457 and 2375±356 for Groups I and II, respectively. Although the mean count rate at the injection site and the sentinel nodes were both higher in Group I of the study compared to Group II (P<0.0001 for both), the mean ratio of sentinel to injection site was statistically higher in Group II (P<0.0001). The 2 days protocol allows that the required lymphoscintigraphy imaging (including delayed views) can be performed before and during operation without any time limits. Most studies have reported similar to ours detection or false negative rates for both protocols. Our study showed comparable mean number of harvested sentinel nodes by the two protocols which is against the hypothesis of moving the tracer to other sentinel nodes by time. Others had similar results. The count rate of the sentinel nodes during surgery was statistically acceptable. Similar results have been reported by others too. Although we didn't evaluate radiation exposure in our study, this was acceptable in other studies and Buscombe et al showed a maximum effective dose of 2.6μSv/MBq for these patients and even assuming this highest value the patient exposure was very low compared to many other procedures. In conclusion, two days protocol gives the sentinel node biopsy team considerable flexibility and lymphoscintigrpahy imaging can be completed before surgery. Finding of the axillary sentinel node during surgery is also being easier. False negative rates as well as the detection rate for one day and two days protocols are comparable.