Rationale: Sarcoidosis is known as a disease with high heterogeneity in clinical severity and inflammatory activity. Based on radiologic criteria Scadding developed a classification system, which is widely used, but is insufficiently for clinical decision making. Therefore, biomarkers and genetic markers, which predict outcome are urgently needed. Objectives and Methods: In order to evaluate such markers we have developed a protocol for classification of different disease courses (sarcoid clinical activity classification (SCAC) based on clinical criteria with 6 categories: 1. acute versus non-acute onset of disease, 2. whether treatment was required or not and 3. need for long term treatment or not. Measurements and Main Results: In total, we evaluated 225 patients with sarcoidosis applying both classification protocols, retrospectively. The described SCAC protocol based on clinical criteria is retrospectively able to stratify patients according to disease outcome. The classes of patients with chronic disease differed significantly regarding pulmonary function test parameters and BAL cell composition. Most interestingly, concentrations of soluble Interleukin-2R (sIL-2R) and neopterin were particularly increased in patients with acute disease, who required long term treatment. A moderate but significant increase of sIL-2R and neopterin was also observed in patients with non-acute disease and need for long term treatment. In contrast to the clinical classification system, the system based on radiologic criteria separates the patients with the need for long term therapy insufficiently, but identifies patients with advanced fibrotic remodeling. Conclusions: the described SCAC protocol is practicable and gives additional information not yet acquired by radiologic typing and seems suitable for studies evaluating genetic influence and biomarkers.