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Background: Although it is relatively common after hematopoietic cell transplant (HCT), graft-vs-host disease (GVHD) is a rare complication following solid organ transplantation (SOT)., Methods: This study evaluated skin biopsy specimens from five cases of SOT GVHD, 15 cases of HCT GVHD, and 15 cases of cutaneous drug eruption. Immunohistochemical staining for CD3, CD4, CD8, T-bet, and GATA-3 was performed to examine the density and immune phenotype of skin-infiltrating lymphocytes., Results: Similar to HCT GVHD, the predominant histopathologic findings in skin biopsy specimens of SOT GVHD were widespread vacuolar interface dermatitis with scattered necrotic keratinocytes. However, the density of dermal inflammation was considerably higher in SOT GVHD. Features that were more predictive of a cutaneous drug eruption over GVHD included spongiosis, confluent parakeratosis, and many eosinophils. Involvement of the hair follicle epithelium was seen in all three disorders. Both forms of cutaneous GVHD showed a predominance of Th1 (CD3+/T-bet+) lymphocytes within the inflammatory infiltrates. This shift was more pronounced in SOT GVHD, particularly among intraepidermal T-cells., Conclusions: SOT GVHD shares many histopathologic features with HCT GVHD. However, SOT GVHD has a greater tendency to develop brisk lichenoid inflammation., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)