Laboratory tests are frequently overused and have elevated inappropriateness rates. We previously developed a model to investigate the rate of utilization of tumor markers (TMs) in outpatients as an indirect indicator of inappropriateness. The model was based on the comparison between the number of actually ordered and expected tests, with the latter estimated on the basis of both epidemiological data and recommendations of available clinical practice guidelines.In this paper we propose an algorithm to distinguish prevalent cases without evidence of disease from those with metastatic spread, on the basis of both epidemiological and clinical information. The algorithm allows for a more precise prediction of the expected TM requests per year, to be compared with the actual number of requested TMs in order to assess possibly inappropriate overordering rates. Moreover, the implementation of the algorithm renders the epidemiologically based model more flexible to develop accurate indicators for appropriateness in the use of TMs in different stages of disease and for different clinical questions. A practical application with CA15.3 requests in breast cancer is presented.