The melanocortin 1 receptor (MC1R) gene plays a key role in the control of melanin formation. Polymorphism in the MC1R gene have been associated with Cutaneous melanoma risk and therefore molecular investigation is essential to prevent the pathology and to reduce melanoma mortality. In the current study, we investigated single nucleotide polymorphism for the MC1R target gene using a miniaturized silicon-based microarray-chip. The microarray substrates were properly designed with a multilayer component (Si/Al/SiO2) to enhance the hybridization optical signal by Al layer acting as a mirror while the SiO2 thickness was optimized for light constructive interference. The microarray probe density was found to be 1.900 ± 200 molecules μm−2. The genotyping experiments performed at different wild type and mutated target amount have shown good sensitivity with discrimination factor >4 for all investigated …