AIM: 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). CONCLUSION: (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