Early detection and proper excision of the primary lesions of malignant melanoma (MM) are crucial for reducing melanoma-related deaths. To support the early detection of melanoma, automated melanoma screening systems have been extensively studied and developed. In this article, we present a hyperspectral melanoma screening system and propose a possible melanoma discrimination index derived from the characteristics of the pigment molecules in the skin, both of which have been derived from hyperspectral data (HSD). The index expresses the disordered nature of each lesion including variegation in color based on variation in spectral information obtained from each lesion. Performance of the index in discriminating melanomas from other pigmented skin lesions has been studied in five cases of melanoma (41 HSD sets), one case of Spitz nevus (13 HSD sets), 10 cases of seborrheic keratosis (78 HSD sets), three cases of basal cell carcinoma (16 HSD sets), and nine cases of melanocytic nevus (21 HSD sets), obtained from patients and volunteers, all of whom were Japanese. Performance of the index, which reflects the disordered nature of a lesion, discriminates melanomas with a sensitivity of 90%, a specificity of 84%, and an area under the receiver operating characteristic curve of 0.93, on resubstitution. An objective melanoma discrimination index at a molecular pigmentary level, derived from HSD, has been proposed, and its performance evaluated. This index was highly successful in discriminating MM from non-melanoma, although the statistical population was small.