Objectives: Disease instability in vitiligo is a prominent step during the development or extension of disease. The presence of marked inflammatory infiltrate may be considered a diagnostic clue for disease instability. However, there is a paucity of literature regarding this. Therefore, the present study was carried out to characterize the nature of inflammatory infiltration in cases of unstable vitiligo. Materials and Methods: Thirty patients of unstable vitiligo diagnosed clinically were enrolled and two biopsies: Lesional and perilesional obtained. Histopathological examination with respect to five parameters, i.e., spongiosis, epidermal lymphocytes, basal cell vacuolation, dermal lymphocytes, and melanophages was done including histological scoring. Immunohistochemical characterization was done for T lymphocytes, Langerhans cells (LCs), macrophages, and B cells by studying their number and distribution. Statistical analysis: Statistical analysis was done using Spearman’s rank coefficient correlation test. Results: Mean T-lymphocytes, macrophages, and LC count were significantly higher in lesional skin. The three parameters correlated with vitiligo histological score. T cells were present more frequently in the dermis and stratum basale. Macrophages were found more in the dermis whereas LC was mainly located in the epidermis. Conclusions: An increase in the population of inflammatory cells, especially T lymphocytes and LC, may serve as an indicator of unstable vitiligo. The relative distribution of these cells points toward signaling between them and their role in the destruction of melanocytes and keratinocytes. A better understanding of the underlying mechanisms may lead to the development of novel targeted therapies.