Gamma probes have been used for sentinel lymph node biopsy in melanoma and breast cancer. However, these probes can provide only radioactivity counts and variable pitch audio output based on the intensity of the detected radioactivity. We have developed a small semiconductor gamma camera (SSGC) that allows visualisation of the size, shape and location of the target tissues. This study is designed to characterise the performance of the SSGC for radioguided surgery of metastatic lesions and for other imaging applications amenable to the smaller format of this prototype imaging system. The detector head had 32 cadmium telluride semiconductor arrays with a total of 1,024 pixels, and with application-specific integrated circuits (ASICs) and a tungsten collimator. The entire assembly was encased in a lead housing measuring 152 mmx166 mmx65 rum. The effective visual field was 44.8 mmx44.8 mm. The energy resolution and imaging aspects were tested. Two spherical 5-mm- and 15-mm-diameter technetium-99m radioactive sources that had activities of 0.15 MBq and 100 MBq, respectively, were used to simulate a sentinel lymph node and an injection site. The relative detectability of these foci by the new detector and a conventional scintillation camera was studied. The prototype was also examined in a variety of clinical applications. Energy resolution [full-width at half-maximum (FWHM)] for a single element at the centre of the field of view was 4.2% at 140 keV ((99m)Tc), and the mean energy resolution of the CdTe detector arrays was approximately 7.8%. The spatial resolution, represented by FWHM had a mean value of 1.56+/-0.05 mm. Simulated node foci could be visualised clearly by the SSGC using a 15-s acquisition time. In preliminary clinical tests, the SSGC successfully imaged diseases in a variety of tissues, including salivary and thyroid glands, temporomandibular joints and sentinel lymph nodes. The SSGC has significant potential for diagnosing diseases and facilitating subsequent radioguided surgery.