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Pembrolizumab can be associated with immune-related cutaneous adverse events, including rare purpuric eruptions that may pose a diagnostic challenge when clinicopathologic findings are inconclusive. While pembrolizumab is generally well tolerated, immune-related adverse events (irAEs) can affect multiple organ systems. Vasculitis is a rare irAE, with heterogeneous clinical presentations ranging from cutaneous purpura to life-threatening systemic involvement. We report the case of a 75-year-old male with a history of myelodysplastic/myeloproliferative neoplasm (MDS/MPN) overlap syndrome and stage IIIA lung adenocarcinoma who developed a widespread purpuric eruption with desquamation shortly after the first cycle of pembrolizumab and subsequent exposure to empagliflozin. Infectious workup was negative. Skin biopsy revealed full-thickness epidermal necrosis with re-epithelialization and mild superficial perivascular lymphocytic infiltrate, findings not typical for leukocytoclastic vasculitis (LCV), which usually shows neutrophilic infiltration, leukocytoclasia, and fibrinoid necrosis of vessel walls. The differential diagnosis included immune-mediated small-vessel vasculitis, severe drug eruption, and Stevens-Johnson syndrome/erythema multiforme spectrum, with empagliflozin representing a significant competing potential trigger given the close temporal relationship to rash onset. The atypical histopathology may be attributed to delayed biopsy and prior systemic corticosteroid treatment, which can obscure classic features of LCV. Pembrolizumab was discontinued, and the patient improved with corticosteroids. This case highlights the diagnostic challenge of evaluating a purpuric and desquamative drug eruption in a patient with competing medication exposures, particularly when biopsy findings are nonspecific or obtained late in the disease course. Clinicians should maintain a high index of suspicion for serious cutaneous adverse reactions in patients receiving immune checkpoint inhibitors who develop purpuric rashes, even in the absence of classic histopathologic features. Early dermatologic evaluation, timely biopsy, and appropriate specimen handling for direct immunofluorescence are critical to guide diagnosis and management. Given the nonspecific histopathologic findings, delayed biopsy, concurrent corticosteroid use, and competing medication exposure, definitive attribution to pembrolizumab could not be established.