In various tumor systems, decreased PO2 values have been demonstrated by various methods. This study addresses the question of whether tumor hypoxia can be found in cutaneous melanoma using lifetime imaging of non-invasive sensors showing phosphorescence quenched by oxygen. Twenty-three cases of cutaneous malignant melanoma (average tumor thickness 1.25 mm, range 0.5-8 mm) were examined using the SkinCam lifetime imaging system for the assessment of cutaneous PO2 levels within the tumors and in adjacent clinically normal skin. For comparison, 30 non-melanoma skin tumors were evaluated. In 15 exploitable melanoma cases, the average hypoxic difference of the lesion compared with the surrounding skin was -10 mmHg, typically associated with an inhomogeneous distribution. Only 10% of the non-melanoma lesions showed a similar hypoxia (false positives). The SkinCam equipment uses a non-invasive imaging method and provides further diagnostic hints in the assessment of benign and malignant skin tumors.