Objective:To obtain a case definition and to describe variables associated with a cluster of unspecific symptoms in healthcare workers (HCW) in a hospital building. Materials and Methods: A cross-sectional study was performed. All people working at the Residencia Cantabria building (a 200-bed building belonging to University Hospital Marqués de Valdecilla) in June 2009 were invited to complete a self-administered questionnaire, including questions on demographic data, working place and shift, working conditions and current symptoms. A cluster analysis was developed to obtain the case definition. The strength of the association between the studied variables and accomplishing the case definition was measured using odds ratios (OR) with the 95% confidence interval (CI). Multiple logistic regression was used to obtain a predictive model; its general validity was estimated with Receiver Operating Curves (ROC) and their Area Under the Curve (AUC). Results: 357 completed questionnaires were obtained. The case was defined as having at least 5 symptoms out of the eleven included. Not being ascribed to a specific shift was the strongest protective variable related with "being a case" (OR = 0.30; 95% CI: 0.17-0.54), whereas the personal antecedent of distal pain or inflammation in arms or legs was the main risk factor (OR = 4.33, 95% CI: 2.75-6.82). A six-variable predictive model has AUC equaling to 0.7378. Conclusions: A disease associated with the indoor environment quality in a hospital was characterized. A multivariate score was drafted for identifying HCW with higher risk of developing the disease in order to apply administrative prevention measures.