Protothecosis is an uncommon human infection caused by achlorophyllic algae of the genus Prototheca, especially P. wickerhamii. The skin is the most frequently involved organ and cases of protothecal tenosynovitis are very rare. A 71-year-old woman without prior medical history except hypertension presented with painful swelling of her right hand that did not improve despite receiving antibiotic treatment. She underwent tenosynovectomy and drainage. Histopathologic examination revealed necrotizing granulomatous inflammation and numerous spherical or morula-like organisms with a spoked wheel appearance. P. wickerhamii was identified from tissue culture. The lesion did not improve with empirical fluconazole therapy. Conventional amphotericin B was administered according to antifungal susceptibility tests and the lesion completely resolved. Protothecosis should be considered in the differential diagnosis for chronic tenosynovitis that does not respond to conventional antibacterial treatment; tissue biopsy with culture is required for diagnosis.