Abstract Introduction The aim of the study was to investigate synovial immunopathology differences between early Behçet disease (BD) and psoriatic arthritis (PsA). Methods Needle arthroscopy of an inflamed knee joint was performed in patients with early untreated BD (n = 8) and PsA (n = 9). Synovial fluid (SF) was collected for cytokines, perforin, and granzyme analysis. Eight synovial biopsies per patient were obtained for immunohistochemical analysis of the cellular infiltrate (T cells, natural killer cells, macrophages, B cells, plasma cells, mast cells, and neutrophils), blood vessels as well as expression of perforin and granzyme. The stained slides were evaluated by digital image analysis. Results The global degree of synovial inflammation was similar in the two types of arthritis. In the analysis of the innate immune cell infiltration, there was a striking neutrophilic inflammation in BD synovitis whereas PsA displayed significantly higher numbers of cells positive for c-kit, a marker of mast cells. As for lymphocytes, CD3 + T cells, but neither CD20 + B cells nor CD138 + plasma cells, were significantly increased in BD versus PsA. Further analysis of the T-lymphocyte population showed no clear shift in CD4/CD8 ratio or Th1/Th2/Th17 profile. The SF levels of perforin, an effector molecule of cytotoxic cells, displayed a significant four- to fivefold increase in BD. Conclusions This systematic comparative analysis of early untreated synovitis identifies neutrophils and T lymphocytes as important infiltrating cell populations in BD. Increased levels of perforin in BD suggest the relevance of cytotoxicity in this disease.