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BACKGROUND: Periostitis, usually seen on X-ray, may be diagnosed on bone scan as non-nodular cortical bone hyperactivity. Both the complete form (including clubbing, arthritis and periostitis) and the incomplete form have been described in association with chronic pulmonary disease, neoplasm, hepatopathy and inflammatory bowel disease. It is not known whether the bone scan pattern of non-nodular cortical bone hyperactivity varies with the etiology. METHODS: We conducted a retrospective study to analyze the etiologies and bone scan patterns of 115 cases of non-nodular cortical bone hyperactivity. RESULTS: Eighty percent of our patients were asymptomatic. Thirty-four percent of all cases of periostitis (all bilateral) were associated with cancer. The rate of cancer in cases of periostitis involving both lower limbs was 28.5%; it was 61.3% when both lower and upper limbs were involved. The duration of the disease was not correlated with either the distribution of periostitis or the intensity of uptake. Moreover, the intensity of uptake was not correlated with the importance of the symptomatology. Bone scan pattern (regular versus heterogenous uptake, localized versus diffuse uptake) was not correlated with the etiology. CONCLUSIONS: Bilateral upper and lower uptake should alert the clinician to the risk of association with neoplasm. Bone scan pattern and intensity of uptake are not necessarily correlated with etiology.