Dermoscopy is considered to be the golden standard for the clinical assessment of pigmented skin lesions. In expert hands, this instrument improves both sensitivity and specificity for the diagnosis of melanoma, however, the outcome is highly dependent on the skills and experience of the examiner. Spectrophotometric intracutaneous analysis (SIAscopy) is a new, commercially available method of analyzing pigmented skin lesions noninvasively. The diagnosis is based on objective features such as the presence of dermal pigment, vascularity of the lesion, and the integrity of collagen. The objective of this study was to examine the usefulness of SIAscopy for the clinical diagnosis of malignant melanoma in a prospective, unbiased manner. We enrolled 65 patients with 83 lesions, where the diagnosis of melanoma could not be ruled out on the basis of the clinical evaluation by a nondermatologist. All lesions were investigated by dermoscopy and SIAscopy and subsequently excised. Histopathologically, 12 lesions were diagnosed as malignant melanoma. Both dermoscopy and SIAscopy overestimated the proportion of possible malignant lesions (n=24 and 41, respectively) and had sensitivities of 92 and 100%, respectively. The specificity of dermoscopy in this study was 81% against 59% for SIAscopy. Our result shows that dermoscopy remains the best diagnostic tool for the preoperative diagnosis of pigmented skin lesions. However, as the SIAscope in addition to the SIAgraph images produces dermoscopic images, it holds the advantages in training and archiving.