Pythiosis is a fatal disease which has high incidence in tropical regions. In contrast with vascular pythiosis, cutaneous and subcutaneous pythiosis are both uncommon. Here, we report a case of subcutaneous pythiosis in a pregnant farmer manifested with a progressively larger and more painful mass at right deltoid. The tissue culture and molecular test were negative for fungi. The diagnosis was supported by the positivity of serum immunochromatographic test (ICT) for pythiosis. Patients responded well to the combination therapy of itraconazole, terbinafine and azithromycin.