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This review discusses the limitations of conventional animal models and two-dimensional cultures in studying cutaneous pigmentary disorders such as vitiligo, melasma, post-inflammatory hyperpigmentation, and solar/senile lentigines. It evaluates advanced in vitro models, including ex vivo explants, co-cultures, three-dimensional skin equivalents, bioprinted constructs, organoids, and skin-on-a-chip platforms. These models are assessed based on their ability to replicate human pigmentation processes, disease-specific pathological processes, and their potential for mechanistic studies and therapeutic evaluation. The review highlights challenges such as vascular and immune integration, long-term stability, and regulatory acceptance, emphasizing the need for improved models within the framework of New Approach Methodologies.