Pathological joint events in both inflammatory arthritis and degenerative arthritis are perpetuated by complex cytokine interactions. Two cytokines, IL-1 and TNF alpha, appear to be the major culprits in the pathogenesis of synovitis and in cartilage damage in these joint diseases. To analyze the expression of IL-1 and TNF alpha and their receptors on synovial and cartilage tissue, we performed an immunohistochemical study on knee biopsies from patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and osteoarthritis (OA). Results identified a prevalent positivity to cytokines and their receptors of synovial cells from RA and PsA with respect to OA patients. In cartilage specimens, most RA and PsA patients showed no expression of the studied receptors, whereas the majority of OA biopsies were positive for all types of examined receptors except IL-1R2. Our study suggests that the cartilage is the main target of these cytokines in OA, while in IA IL-1 and TNF alpha exert their action in synovial tissue. In all the studied pathologies (RA, PsA, OA) the synovial tissue and the cartilage were differentially involved, indicating the importance of investigating both structures in joint disease studies.