10% of > 55-year-old adults suffer some kind of non-neoplastic knee pain and 75% of the musculoskeletal neoplastic disease develops in the knee. to identify clinical characteristics of knee pain in neoplastic knee pathology. after appropriate authorization of the Local Committee of Investigation and under informed consent, we made a crosssectional and a risk analysis study. We included 160 patients who were seeking medical help due to knee pain. They answered a standardized questionnaire relating to the characteristics of their pain symptomatology. Data were integrated into two groups with knee pain; a) neoplasic (cases, n = 65), b) non-neoplasic (controls, n = 95) and analyzed (SPSS v.15™). We used homogeneity tests between groups (p > 0.05); inferential analysis (Student t test, χ(2)) and risk assessment (OR), p ≤ 0.05, (CI 95%), Statistical power was > 0.80. female gender predominated (55%); age was 40.3 ± 19.6 years. The most prevalent diagnoses were knee osteoarthritis 37% for non-neoplasic group; giant cell tumor 10% for benign neoplasic group and osteosarcoma 6.1% for neoplasic malignant group. Knee pain lasting < 4 months (OR 7.6; CI 95% 3.48-16.5) and severe intensity (OR 5.7; CI 95% 2.82-11.64), constant pain (OR 2.9; CI 95% 1.37-6.36), rapidly progressive fluctuation (OR 31; CI 95% 7.01-137) and nocturnal predominance (OR 7.72; CI 95% 3.2-18.5) were characteristics of neoplasic knee pain. the neoplasic knee pain was characterized for a rapid onset, severe and constant pain, progressive, fluctuation and predominantly by night-time.