A non-invasive tool for skin disease diagnosis would be a useful clinical adjunct. The purpose of this study was to determine whether visible/near-infrared spectroscopy can be used to non-invasively characterize skin diseases. In-vivo visible- and near-infrared spectra (400-2500 nm) of skin neoplasms (actinic keratoses, basal cell carcinomata, banal common acquired melanocytic nevi, dysplastic melanocytic nevi, actinic lentigines and seborrheic keratoses) were collected by placing a fiber optic probe on the skin. Paired t-tests, repeated measures analysis of variance and linear discriminant analysis were used to determine whether significant spectral differences existed and whether spectra could be classified according to lesion type. Paired t-tests showed significant differences (p<0.05) between normal skin and skin lesions in several areas of the visible/near-infrared spectrum. In addition, significant differences were found between the lesion groups by analysis of variance. Linear discriminant analysis classified spectra from benign lesions compared to pre-malignant or malignant lesions with high accuracy. Visible/near-infrared spectroscopy is a promising non-invasive technique for the screening of skin diseases.