Rare diseases place a high burden on society as they are often associated with significant disability, potential years of life lost, high rate of hospitalization and admission to long-Term care, high cost of illness and immense mortality rate. Effective screening approaches followed by verification with genetics analysis would be crucial for early diagnosis and treatment in order to prevent complications and decrease the disease burden. This study proposes development and clinical validation of rare skin diseases early screening System for identification of rare disease groups followed by multimodal spectroscopic dermoscopic evaluation. For image acquisition an imaging prototype was used utilizing 526 nm, 663 nm and 964 nm multispectral LEDs for diffuse reflectance imaging and 405 nm LEDs for autofluorescence excitation, as well as Nuance multispectral imaging camera with spectral range 450-950 nm. Spectral reflectance and autofluorescence images were analyzed to determine informative/efficient parameters suitable for identification and diagnostics of rare diseases. © 2023 SPIE .