We describe a case of Penicillium marneffei infection acquired in Thailand, manifesting as an immune reconstitution inflammatory syndrome (IRIS) in a Caucasian man with advanced HIV-related immunosuppression (CD4 72 cells/mm³). Initial presentation was consistent with Pneumocystis jirovecii pneumonia, and empirical co-trimoxazole resulted in clinical improvement. One month after initiating antiretroviral therapy (ART), an enlarging scaly lesion on his forehead and erythematous nodules on his face, trunk and limbs developed. P. marneffei was isolated from a skin aspirate. Response to antifungal therapy was complicated by drug interactions but cure was complete after four months of treatment. Few cases of IRIS associated with P. marneffei have been reported.