We report the case of a 52-year-old male heart transplant recipient with a persistent localized subcutaneous infection by Scedosporium apiospermum. This form differs from the most common mycetoma by the absence of granules. The patient showed multiple nodules on the right hand that were surgically removed. Concomitantly, he received oral itraconazole, but the infection persisted for two years, and several surgical interventions were necessary to eradicate the infection. Our case demonstrates that a medical approach alone may be not sufficient to cure this fungal infection.