Although numerous studies have been performed to fabricate various optical tissue phantom (OTP) models, the fabrication of OTPs that simulate skin layers is laborious and time-consuming owing to the intricate characteristics of skin tissue. This study presents various OTP models that optically and structurally simulate the epidermis–dermis skin layer. The spin-coating method was employed to reproduce a uniform thin layer that mimics the epidermis layer, and the fabrication parameters were optimized for epoxy and silicone reference materials. Various OTP models simulating blood vessels and hyperpigmentation lesions were fabricated using the two reference materials to determine their feasibility. The suitability of each of the two reference materials for OTP fabrication was qualitatively evaluated by comparing the quality of the OTP models.