As the incidence of skin cancer is still increasing worldwide, there is a high demand for early, non-invasive and inexpensive skin lesion diagnostics. In this article we describe and combine two skin imaging methods: skin autofluorescence (AF) and multispectral criterion p’. To develop this method, we used custom made prototype with 405 nm, 526 nm, 663 nm and 964 nm LED illuminations, perpendicular positioned linear polarizers, 515 nm filter and IDS camera. Our aim is to develop a skin lesion diagnostic device for primary care physicians who do not have experience in dermatology or skin oncology. In this study we included such common benign lesion groups as seborrheic keratosis, hyperkeratosis, melanocytic nevi and hemangiomas, as well two types of skin cancers: basal cell carcinoma and melanoma. By combining skin AF and multispectral p’ imaging methods, we achieved 100% sensitivity and 100% specificity for distinguishing melanoma (3 histologically confirmed cases) from seborrheic keratosis (13 dermatologically confirmed cases), hyperkeratosis (8 histologically and 1 dermatologically confirmed case), melanocytic nevi (23 dermatologically confirmed cases ), basal cell carcinomas (2 histologically and 16 dermatologically confirmed cases) and hemangiomas (8 dermatologically confirmed cases). Unfortunately, currently this method cannot distinguish the basal cell carcinoma group from benign lesion groups.