We conducted the current study to evaluate the cases of fever of unknown origin (FUO) admitted in our institution during the 10 years between 1991 and 2001 and to compare the patients diagnosed as having adult-onset Still disease (AOSD) with the patients with FUO due to other diagnoses. We performed a case-control study and analyzed 26 patients with AOSD and 135 patients with FUO due to other diseases. Controls were classified into 1 of 4 groups: 1. Infectious diseases; 2. Malignant conditions; 3. Autoimmune diseases; 4. No diagnosis. Differences between groups were evaluated by analysis of variance (ANOVA). Odds ratios (OR) were calculated by multiple logistic regression analyses. Patients with AOSD were younger than controls. Arthritis (OR, 8.6; 95% confidence interval [CI], 1.5-49.1; p = 0.014), pharyngitis (OR, 6.9; 95% CI, 1.5-30.2; p = 0.010), splenomegaly (OR, 5.4; 95% CI, 1.1-26.7; p = 0.039), and neutrophilic leukocytosis (OR, 18.1; 95% CI, 3.5-93.6; p = 0.001) were significantly more common in patients with AOSD than in the control groups. A clinical scale that identifies patients with AOSD was designed. It proved to be highly specific ( approximately 98%), with predictive values greater than 90%.AOSD is a defined clinical entity. In most cases, it is clinically distinguishable from other causes of FUO. We propose a clinical scale as a tool to identify patients whose disease can be diagnosed based on clinical grounds without the need of long, costly diagnostic procedures.