Axillary lymph node dissection (ALND) in the treatment of breast cancer is essential for predicting the prognosis and regional control of the tumor. At the same time ALND is associated with pain, numbness and sometimes lymphedema. Sentinel lymph node biopsy (SLNB) is a potential alternative procedure to conventional ALND in clinically node-negative breast cancer. In this study, we prepared the technetium-99m-labeled tin colloids with different sizes and compared their efficacy in SLNB. From September 1998 to February 2002, 184 clinically node-negative breast cancer patients were enrolled in the study at Keio University Hospital. Sentinel lymph nodes (SLNs) were identified by both blue dye and radioisotope. We prepared small-sized technetium-99m-labeled tin colloid (particle size: 200-400 nm in diameter). Regular-sized technetium-99m-labeled tin colloid is 400-1000 nm in diameter. In 74 patients, a SLNB was performed using regular-sized tin colloid; small-sized tin colloid was used in 110 patients. Subsequently, all of the patients were immediately followed by ALND. All dissected lymph nodes were evaluated by routine histopathological examination. The clinicopathological characteristics of the two groups were comparable. The lymphoscintigram detected SLN more frequently in the small-sized colloid group than in the regular-sized colloid group (P < 0.01). Small-sized tin colloid was also superior to regular-sized tin colloid in the SLN identification rate (97.3% versus 86.5%; P = 0.01). The mean value for ex vivo counts of the hottest sentinel lymph nodes of the small-sized colloid group was significantly higher than the counts of the regular-sized colloid group (P < 0.01). There was no significant difference in the accuracy between the two groups. It was concluded that SLNB using the small-sized tin colloid was technically feasible and provided higher detection and identification rates than the regular-sized tin colloid.