This study was designed to identify the frequency of internal mammary drainage in patients undergoing sentinel lymph node (SLN) lymphoscintigraphy in a controlled clinical trial. The practicability and relevance of internal mammary SLN biopsy as a method to improve nodal staging and treatment in breast cancer were investigated. A total of 707 evaluable patients with invasive breast cancer underwent SLN biopsy based on lymphoscintigraphy, intraoperative g probe detection, and blue dye mapping using technetium Tc 99m albumin colloid and Patent Blue V injected peritumorally. This was followed by standard axillary treatment in the same operation in all patients. Lymphoscintigraphy showed internal mammary sentinel nodes in 62 patients (9%), and internal mammary drainage was identified perioperatively in an additional 7 patients (1%) using g probe detection. Sampling of the internal mammary basin, based on the results of lymphoscintigraphy and g probe detection, was done in 31 of 69 patients (45%). One patient had a pneumothorax and 2 experienced bleeding during internal mammary sampling. Internal mammary metastases were detected in 4 of 31 patients (13%). In 2 of the patients (6%), internal mammary nodes (IMNs) showed metastatic involvement without accompanying axillary metastases. One of these 2 patients would have received adjuvant endocrine systemic therapy because of the characteristics of the tumor, but may not have been recommended to receive adjuvant chemotherapy. Sampling of the internal mammary basin led to a change of management in these 2 patients, ie, institution of adjuvant chemotherapy. Therefore, a change in management occurred in only 2 of the 69 patients in our series, but 38 patients with unbiopsied "hot" IMNs remained with unknown internal mammary status. Biopsy of IMNs alters staging in few patients, and the impact on indication for adjuvant treatment was low. Internal mammary SLN biopsy may be associated with some additional morbidity. Current evidence suggests that internal mammary SLN biopsy is still a research tool.