Soft tissue infections are common in patients with end-stage renal failure, particularly those with concomitant diabetes and peripheral vascular disease. They usually affect the lower extremities and their microbiology is dominated by gram-positive organisms. Empirical antibiotic treatment is usually straightforward, and success or failure is heavily influenced by the degree of underlying vascular disease. We present an unusual case of treatment-resistant and eventually fatal soft tissue infection of the shoulder in a maintenance haemodialysis patient with known chronic lymphocytic leukaemia (CLL). We discuss the case with emphasis on the differential diagnosis of unusual soft tissue infections in a dialysis patient. We review possible causes of treatment failure, unusual organisms and implications for treatment.