The knee is a frequent target for gout and calcium pyrophosphate dihydrate (CPPD) disease with involvement of both articular and peri-articular structures. The aims of the present study were to investigate the relationship between clinical and ultrasound (US) findings and to describe the prevalence and distribution of crystal deposits in the knee in patients with gout and CPPD disease. Thirty patients with gout and 70 patients with CPPD disease were enrolled in the study. Prior to US assessment all patients underwent a clinical examination by an expert rheumatologist who recorded the presence/absence of pain, tenderness (evocated by palpation and/or active or passive mobilisation of the knee), and knee swelling. US examinations were performed using a Logiq 9 (General Electric Medical Systems, Milwaukee, WI) equipped with a multifrequency linear probe, working at 9 MHz. Two hundred knee joints were investigated in a total of 100 patients. Fifty-one (25.5%) knee joints were found clinically involved, while at least one US finding indicative of joint inflammation was obtained in 73 (36.5%) knee joints.The most frequent US finding indicative of knee joint inflammation was joint effusion, detected in 21 (35%) out of 60 knees and in 52 (37%) out of 140 knees, in gout and CPPD disease, respectively. Ten (17%) out of 60 knees and 21 (15%) out of 140 knees were found positive for synovial hypertrophy with or without intra-articular power Doppler, in gout and CPPD disease respectively. Sonographic evidence of crystal deposition within joint cartilage (hyaline and fibrocartilage) was more frequently seen than in the soft tissue in the knee.This study demonstrated that US detected a higher number of inflamed knee joints than clinical assessment in patients with crystal related arthropathies and that the distribution of crystal deposits at joint cartilage level permitted distinction between gout and CPPD disease. Further studies are required to investigate both sensitivity and specificity of US features indicative of crystal aggregates at both tendon and entheseal level.