It has been shown that optical phantoms are able to simulate important optical parameters of biological tissues, such as refractive index, absorption coefficient, scattering coefficient, and anisotropy.3 A typical optical phantom is composed of the base, the scattering, and the absorption materials. On some occasions, fluorophores and other contrast enhancement agents are also added in the phantoms.4 Optical phantoms have been developed and widely used in various clinical applications, such as medical device calibration, validation, and clinical education. One example is to use brain-simulating phantoms to simulate brain structural and physiological properties to calibrate spectrophotometric devices for brain functional studies.5,6 Existing optical phantoms are based on homogenous materials without considering the multilayered heterogeneous structures observed in biological tissue. Optical measurements calibrated by such a phantom may have limited accuracy and traceability. To simulate actual tissue conditions, multilayered phantoms have been fabricated recently using various methods, such as multilayered curing,7 integration after mold casting,8 and spin coating.9 However, these methods have their own limitations and can hardly simulate both structure and optical heterogeneities observed in various biological tissue types.10,11 For example, multilayered curing and mold casting methods are able to produce large phantoms, but can hardly simulate tissue structural heterogeneity. Spin coating method is able to produce thin phantoms that simulate human skin, but cannot simulate large tissues with embedded anomalies. Since these phantoms cannot effectively simulate tissue heterogeneity, using them to calibrate spectral optical devices may not improve the measurement reliability in biologic tissue.