Improvements in the specificity of radiopharmaceutical compounds have been paralleled by an upsurge of interest in developing small detectors to assist surgeons in localizing tumour tissue during surgery. This study reports the main technical features and physical characteristics of a new hand-held gamma camera dedicated to accurate and real-time intra-operative imaging. First clinical experience is also reported. The POCI (Per-operative Compact Imager) camera consists of a head module composed of a high-resolution interchangeable lead collimator and a CsI(Na) crystal plate optically coupled to an intensified position-sensitive diode. The current prototype has a 40-mm diameter field of view, an outer diameter of 9.5 cm, a length of 9 cm and a weight of 1.2 kg. Overall detector imaging characteristics were evaluated by technetium-99m phantom measurements. Three patients with breast cancer previously scheduled to undergo sentinel lymph node detection were selected for the preliminary clinical experience. Preoperative images of the lymphatic basin obtained using the POCI camera were compared with conventional transcutaneous explorations using a non-imaging gamma probe. The full-width at half-maximum (FWHM) spatial resolution was investigated in both air and scattering medium; when the phantom was placed in contact with the collimator, the POCI camera exhibited a 3.2 mm FWHM. The corresponding sensitivity was 290 cps/MBq. The preliminary clinical results showed that POCI was able to predict the number and location of all SLNs. In one case, two deep radioactive nodes missed by the gamma probe were detected on the intra-operative images. This very initial experience demonstrates that the physical performance of the POCI camera is adequate for radio-guided surgery. These results are sufficiently encouraging to prompt further evaluation studies designed to determine the specific and optimal clinical role of intra-operative imaging devices.