Hyperspectral imaging (HSI) allows the identification of objects through the analysis of their unique spectral signatures. Although first developed many years ago for use in terrestrial remote sensing, this technology has more recently been studied for application in the medical field. With preliminary data favoring a role for HSI in distinguishing normal and lesional skin tissues, we sought to investigate the potential use of HSI as a diagnostic aid in the classification of atypical Spitzoid neoplasms, a group of lesions that often leave dermatopathologists bewildered. One hundred and two hematoxylin and eosin-stained tissue samples were divided into 1 of 4 diagnostic categories (Spitz nevus, Spitz nevus with unusual features, atypical Spitzoid neoplasm, and Spitzoid malignant melanoma) and 1 of 2 control groups (benign melanocytic nevus and malignant melanoma). A region of interest was selected from the dermal component of each sample, thereby maximizing the examination of melanocytes. Tissue samples were examined at ×400 magnification using a spectroscopy system interfaced with a light microscope. The absorbance patterns of wavelengths from 385 to 880 nm were measured and then analyzed within and among groups. All tissue groups demonstrated 3 common absorbance spectra at 496, 533, and 838 nm. Each sample group contained at least one absorption point that was unique to that group. The Spitzoid malignant melanoma category had the highest number of total and unique absorption points for any sample group. The data were then clustered into 12 representative spectral classes. Although each of the sample groups contained all 12 spectral vectors, they did so in differing proportions. These preliminary results reveal differences in the spectral signatures of the Spitzoid lesions examined in this study. Further investigation into a role for HSI in classifying atypical Spitzoid neoplasms is encouraged.