Objectives: To describe and identify factors, in clinical practice, that might be useful increasing the index of suspicion for diffuse idiopathic skeletal hyperostosis (DISH), at a relatively young age. Design: A group of 18 patients with DISH (12.8) who were diagnosed before the age of 50 years (group A) was compare with a group of 20 patients of similar age with osteoarthritis (group B), and 24 patients with DISH diagnosed after the age of 60 years (group C). Data collection included demographic characteristics, body region of main complaint evidence for enthesopathies or tendonitis, length of follow-up, body mass index (BMI), serum lipid profile, family history of diabetes mellitus (DM), and hypertension (HTS). The presence of concomitant diseases and use of medications was recorded at presentation and during the follow-up period. Results: Patients in group A compared with group B, had statistically significant more pain in the lumbar and thoracic spine (P = 0.001 and 0.016, respectively), tendon itis/enthesopathies (P=0.004), obesity (BMI >= 30, P=0.014), and first degree relative with HTS and DM (P=0.015 and 0.05, respectively). By the end of the follow-up, significantly more patients in group A were affected by DM compared with group B (P=0.007). Conclusions: Individuals in the fifth decade of life are likely to be affected by DISH if they are obese, have a first degree relative with either HTS or DM, complain of lumbar or thoracic spinal pain, and are affected by enthesopathies or tendonitis. The likelihood of relatively young patients with >= 3 clinical parameters to be affected with DISH, was six times higher than age and sex matched controls (P = 0.004). (C) 2008 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.