OBJECTIVE We evaluated the usefulness of (99m)Tc-tetrofosmin axillary pinhole (P)-SPECT in breast cancer (BC) non palpable axillary lymph node metastasis detection compared with conventional planar and SPECT scintimammography. METHODS We studied prospectively 188 consecutive patients with suspected primary BC, negative at axillary clinical examination. Ten minutes after 740 MBq (99m)Tc-tetrofosmin injection, planar and SPECT scintimammography were acquired, followed by axillary P-SPECT imaging. RESULTS At histology, 12 patients had benign mammary lesions and 176 had BC. Axillary lymph node dissection (ALND) was performed in all BC patients, bilaterally in 3 cases: 74/179 axillae had metastases. P-SPECT showed a significantly higher overall sensitivity than SPECT and planar (93.2% vs 85.1% and 36.5%, respectively; p<0.05 and p<0.0005, respectively) and was false negative in 5 patients with 1 metastatic node each, micrometastatic in 4/5 cases; SPECT and planar were also false negative in these 5 cases and in 6 and in 42 further cases, respectively. P-SPECT added important prognostic information by distinguishing single from multiple and pound 3 from >3 nodes; only P-SPECT defined the exact number of nodes in 15/25 patients with 2-4 nodes. P-SPECT showed the highest accuracy and NPV: 92.7% and 95%, respectively (SPECT 90.5% and 90%, respectively; planar 73.2% and 68.9%, respectively). CONCLUSIONS (99m)Tc-tetrofosmin axillary P-SPECT appears highly accurate in BC non palpable axillary lymph node metastasis detection and significantly more sensitive than both planar and SPECT, its few false negative results predominantly concerning micrometastases; moreover, only P-SPECT gave additional important prognostic information. Given its very high NPV, P-SPECT could also be used to better select patients who might avoid ALND.