The recently introduced SPECT/CT integrates the physiologic data of SPECT with the anatomic data of CT into a single image. The purpose of this pilot study was to explore the additional value of SPECT/CT in breast cancer patients and melanoma patients with inconclusive planar image findings. Thirty-one patients had planar lymphoscintigrams showing unexpected lymphatic drainage, 6 had lymphoscintigrams that were difficult to interpret, and 3 showed no drainage on planar imaging. SPECT/CT was performed immediately after delayed planar imaging. In 4 patients, SPECT/CT showed 6 additional sentinel nodes, of which 2 were tumor-positive and led to upstaging and tailored management in 5% of patients. SPECT/CT depicted sentinel nodes in 3 patients whose delayed planar imaging had shown no drainage. SPECT/CT was of additional value in finding the exact anatomic location of sentinel nodes in patients with inconclusive planar image findings. SPECT/CT also detected sentinel nodes in addition to those found on planar images, and SPECT/CT detected sentinel nodes in patients whose planar images had shown none.