An essential prerequisite for a successful sentinel node biopsy (SNB) procedure is an accurate map of the pattern of lymphatic drainage from the primary tumor site. The role of lymphoscintigraphy (LS) in SNB is to provide such a map in each patient. This map should indicate not only the location of all sentinel nodes but also the number of SNs at each location. Such mapping can be achieved using 99mTc-labeled small particle radiocolloids, high-resolution collimators with minimal septal penetration, and imaging protocols that detect all SNs in every patient regardless of their location. This is especially important in melanoma patients, since high-quality LS can identify the actual lymphatic collecting vessels as they drain into each SN. The SN is not always found in the nearest node field and is best defined as "any lymph node receiving direct lymphatic drainage from a primary tumor site." Reliable clinical prediction of lymphatic drainage from the skin or breast is not possible. Patterns of lymphatic drainage from the skin are highly variable from patient to patient, even from the same area of the skin. Unexpected lymphatic drainage has been found from the skin of the back to SNs in the triangular intermuscular space and in some patients through the posterior body wall to SNs in the para-aortic, paravertebral, and retroperitoneal areas. Lymphatic drainage from the head and neck frequently involves SNs in multiple node fields, and can occur from the base of the neck up to nodes in the occipital or upper cervical areas or from the scalp down to nodes at the neck base, bypassing many other node groups. Lymphatic drainage from the upper limb can be directly to SNs above the axilla. Drainage to the epitrochlear region from the hand and arm is more common than was previously thought as is drainage to the popliteal region from the foot and leg. Interval nodes, which lie along the course of a lymphatic vessel between a melanoma site and a recognised node field, are not uncommon especially on the trunk. Drainage across the midline of the body is quite frequent on the trunk and in the head and neck region. In breast cancer, although dynamic imaging is usually not possible, an early postmassage image will also often visualize the lymphatic vessels leading to the SN allowing them to be differentiated from any second tier nodes. Small radiocolloid particles are also needed to achieve migration from peritumoral injections sites and LS allows accurately detection of SNs outside the axilla, which occur in about 50% of patients. These nodes may lie in the internal mammary chain, the supraclavicular region, or the interpectoral region. Intramammary interval nodes can also be SNs in some patients. The location of the cancer in the breast is not a reliable guide to lymphatic drainage, since lymph flow often crosses the center line of the breast. Micrometastatic disease can be present in any SN regardless of its location, and for the SNB technique to be accurate all true SNs must be identified and removed in every patient. LS is an important first step in ensuring that this goal is achieved.