Scintigraphy with 1123-N-(2-Diethyl aminoethyl) 4-Iodobenzamide (I123-IDAB), a radiolabeled benzamide, has recently been introduced to visualize sigma receptors in vivo. In this study we evaluated the potential clinical applicability of I123-IDAB scintigraphy in patients with melanoma and in patients with non-small cell lung carcinoma (NSCLC); tumors in which sigma receptors are expressed. Twenty-six patients with a history of malignant melanoma and 8 patients with proven NSCLC were studied. Whole body scintigraphy was performed 4-5 hours after the injection of 170 MBq of I123-IDAB. All patients with ocular lesions and those with NSCLC underwent SPECT imaging of the head or thorax, respectively. For other patients additional spot- and or SPECT scans of suspected regions were acquired if necessary. Three patients with a history of malignant melanoma were considered to be in complete remission. None presented abnormalities on the I123-IDAB scintigraphy. In 20 of the 23 patients (87%) with proven melanoma, lesions were identified on the I123-IDAB scintigraphy. On a lesion site basis the sensitivity averaged 64% (43/67) Lesions located in the liver and those originating from an amelanotic melanoma could not be detected, while a sensitivity of 89% was observed for ocular sites when SPECT was used. In patients with NSCLC all primary lesions showed an increased uptake of tracer, but only 4 out of 18 (22%) mediastinal lymph nodes that were suspected radiologically. I123-IDAB scintigraphy can be used to visualize melanoma and NSCLC lesions in vivo. In malignant melanoma this may be useful to confirm the melanoma nature of lesions that are not easily accessible to biopsy. Differences in sensitivity between the various sites however must be kept in mind when interpreting the I123-IDAB scintigraphy. In patients with NSCLC the value of I123-IDAB SPECT is at least questionable.