Actinomycosis is a chronic, opportunistic infection caused by Actinomyces species, such as Actinomyces bacillus. Actinomycosis in long bones is very rare. To the best of our knowledge, isolated primary actinomycosis of the humerus is rarely reported in literature. We present a rare case of a refractory primary actinomycosis of the humerus. A 66-year-old man with no history of concomitant conditions was admitted to our hospital with a history of a tumour on the distal third of the left arm as a result of a closed trauma without fracture 20 years before. Pathological anatomy samples showed the presence of Actinomyces. Cultures were subjected to a prolonged incubation of 21 days under aerobic and anaerobic conditions and were always negative. He underwent several surgical procedures and received long-term antibiotic therapy with poor outcome. Primary actinomycosis in long bones is uncommon. Diagnosis may be challenging: considering the small number of case studies reported in the literature, symptoms are not specific, and the organism is difficult to isolate. Antibiotic treatment may not be sufficient to improve the clinical condition, and surgical alternatives should be considered.