<jats:sec><jats:title>Purpose:</jats:title><jats:p>The authors assembled a prototype compact gamma‐ray imaging probe (MediPROBE) for sentinel lymph node (SLN) localization. This probe is based on a semiconductor pixel detector. Its basic performance was assessed in the laboratory and clinically in comparison with a conventional gamma camera.</jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p>The room‐temperature CdTe pixel detector (1 mm thick) has<jats:inline-graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="graphic/mp5034-math-0001.png" xlink:title="urn:x-wiley:00942405:mp5034:equation:mp5034-math-0001" /> square pixels arranged with a <jats:inline-graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="graphic/mp5034-math-0002.png" xlink:title="urn:x-wiley:00942405:mp5034:equation:mp5034-math-0002" /> pitch (sensitive area <jats:inline-graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="graphic/mp5034-math-0003.png" xlink:title="urn:x-wiley:00942405:mp5034:equation:mp5034-math-0003" />), coupled pixel‐by‐pixel via bump‐bonding to the Medipix2 photon‐counting readout CMOS integrated circuit. The imaging probe is equipped with a set of three interchangeable knife‐edge pinhole collimators (0.94, 1.2, or 2.1 mm effective diameter at 140 keV) and its focal distance can be regulated in order to set a given field of view (FOV). A typical FOV of 70 mm at 50 mm skin‐to‐collimator distance corresponds to a minification factor 1:5. The detector is operated at a single low‐energy threshold of about 20 keV.</jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p>For<jats:inline-graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="graphic/mp5034-math-0004.png" xlink:title="urn:x-wiley:00942405:mp5034:equation:mp5034-math-0004" />, at 50 mm distance, a background‐subtracted sensitivity of <jats:inline-graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="graphic/mp5034-math-0005.png" xlink:title="urn:x-wiley:00942405:mp5034:equation:mp5034-math-0005" /> and a system spatial resolution of 5.5 mm FWHM were obtained for the 0.94 mm pinhole; corresponding values for the 2.1 mm pinhole were <jats:inline-graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="graphic/mp5034-math-0006.png" xlink:title="urn:x-wiley:00942405:mp5034:equation:mp5034-math-0006" /> and 12.6 mm. The dark count rate was 0.71 cps. Clinical images in three patients with melanoma indicate detection of the SLNs with acquisition times between 60 and 410 s with an injected activity of 26 MBq <jats:inline-graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="graphic/mp5034-math-0007.png" xlink:title="urn:x-wiley:00942405:mp5034:equation:mp5034-math-0007" /> and prior localization with standard gamma camera lymphoscintigraphy.</jats:p></jats:sec><jats:sec><jats:title>Conclusions:</jats:title><jats:p>The laboratory performance of this imaging probe is limited by the pinhole collimator performance and the necessity of working in minification due to the limited detector size. However, in clinical operative conditions, the CdTe imaging probe was effective in detecting SLNs with adequate resolution and an acceptable sensitivity. Sensitivity is expected to improve with the future availability of a larger CdTe detector permitting operation at shorter distances from the patient skin.</jats:p></jats:sec>