The aim of the present study was to assess the feasibility of a portable gamma camera (PGC) for guiding surgical treatment in locally advanced breast cancer (LABC) after neoadjuvant therapy (NT). Since January 2012, a PGC (Sentinella 102, ONCOVISION) has been available in our center. We planned to perform a feasibility monocentric prospective study involving 15-20 patients with LABC for assessing the diagnostic performance of this PGC after NT (Breast Cancer Surgery-S102). Before the surgical treatment and at the end of NT an injection of 99mTc-Sestamibi (100-150 MBq) was made. Conventional scintimmamography (SMM) and Sentinella 102 images were obtained from 18 patients. 10 (55.5 %) patients showed a focal uptake of tracer in the breast or lymph nodes before or after the surgical excision (on histological specimen), while 8 did not. The histological specimen concluded for a complete response to NT in 4 (22.2 %) patients and for a partial or no response to treatment in the remnant 14 subjects. The specificity and false-negative rate of the Sentinella 102 compared to SMM were 100 % for both and 38 % vs. 60 %, respectively. The global diagnostic accuracy of Sentinella 102 was: 66.7 % (95 % confidence interval: 44.88-88.44 %). The present feasibility study shows how a new nuclear imaging device can be useful in the operating theatre for guiding a radical surgery approach in patients with LABC after NT.