Aims and background The extent of axillary lymph node dissection for breast cancer treatment is tailored to each patient. When the surgeon assumes that full dissection, including level III, is needed, there are basically two ways for reaching the apical nodes while preserving the pectoralis muscles: a subpectoral approach, below the joined pectoralis muscles, and another that includes an additional interpectoral dissection between the muscles. We conducted a study to evaluate the radicality of dissection using these two approaches. Methods To determine whether the harvest of level III axillary lymph nodes is equivalent with the different approaches, we prospectively studied 75 patients with breast cancer. Careful axillary lymph node dissection was done to as radical an extent as possible, first below the lateral edge of the joined pectoralis muscles (subpectoral approach) and sequentially after opening the space between the muscles (additional interpectoral approach). The number of patients with extra level III nodes retrieved by the addition of an interpectoral dissection as well as the number of complementary nodes obtained in such patients were determined. Results We excised 1701 axillary lymph nodes in 75 patients (mean, 22.7). Using first the subpectoral approach, we resected 259 level III nodes in 68 patients (mean, 3.8); in 56 patients, we removed 132 additional level III nodes using the supplementary interpectoral approach (mean, 2.4). In 7 patients (9.3%), we found at least one metastatic node with the interpectoral approach. Two of these patients had positive level III nodes that were discovered only by addition of the interpectoral dissection. Conclusions The dissection of level III axillary nodes is more radical when an additional interpectoral dissection is performed after a subpectoral approach has been used. The exclusive subpectoral approach frequently leaves residual nodes at the apex of the axilla.