Novel optical spectroscopy and imaging methods may be valuable in the early detection of cancer. This paper reports differences in the luminescence responses of pigmented skin lesions (melanomas and nevi) and apparently normal non-pigmented human skin, based on analyses of synchronous luminescence spectroscopy measurements. Measurements were performed in the excitation range of 330-545 nm, with synchronous intervals varying from 30-120 nm. Normal skin, nevi, and melanomas differ in the way they fluoresce, and these differences are more distinct in the synchronous fluorescence spectra than in the conventional emission and excitation spectra. The differences in the fluorescence characteristics of pigmented and normal skin samples were ascribed to differences in concentrations of endogenous fluorophores and chromophores. Principal component and linear discriminant analysis of the synchronous spectra measured at different synchronous intervals showed that the greatest variance among the sample groups was at the 70 nm interval spectra. These spectra were then used to create partial least squares discriminant analysis-based classification models. Evaluation of the quality of these models from the receiver operating characteristic curves showed they performed well, with a maximum value of 1 for the area under the curve for melanoma detection. Hence, synchronous luminescence spectroscopy coupled with statistical methods may be advantageous in the early detection of skin cancer.