It appears that prognostic factors of proven value in the management of other malignancies have marginal value in the treatment of patients with squamous cell carcinomas of the head and neck (SCCHN). For example, age, sex, and performance status do not correlate with treatment outcome. Similarly, histologic differentiation has little predictive value, with undifferentiated carcinomas of nasopharyngeal origin being a possible exception. On the other hand, primary tumor site may be an important prognostic factor, with tumors arising from the nasopharynx, oral cavity, and possibly the oropharynx having a more favorable outcome, whereas tumors of the hypopharynx appear to be the least favorable. A tumor's TNM stage is also highly predictive of response to treatment and survival. Overall stage of disease is an effective predictor of relapse and survival only for patients with limited disease and only after the primary site is specified. Independent of primary tumor site, an inverse correlation clearly exists between T and N stage and either response to treatment or overall survival. Flow cytometry, a relatively new test, appears to be one of the most significant predictors of response to chemotherapy, relapse, and survival in patients with SCCHN. As a prognostic factor, DNA tumor content may be independent of all other known clinical and pathologic factors. Patients with diploid tumors have a superior relapse-free and overall survival as compared with patients whose tumors are aneuploid. Another parameter of significant value is the patient's response to induction chemotherapy, with responding patients demonstrating a far superior relapse-free and overall survival compared with nonresponders. In summary, the site of the primary tumor, its T stage, N stage, and DNA content, and the magnitude of its response to induction chemotherapy are the most valuable prognostic factors in SCCHN. It is assumed, however, that as new and more effective therapies are developed for patients with SCCHN, previously significant prognostic factors will cease to have clinical or scientific value. Similarly, as new diagnostic tests and staging tools are developed, a new generation of prognostic factors with greater biologic and clinical relevance is likely to emerge. In the evolution of new therapies for patients with SCCHN, prognostic factors such as those mentioned here or ones yet to be evaluated will be central to the design of clinical studies and the identification of specific patients for specific therapies. Once treatment is initiated, treatment-related prognostic factors may further identify patients for whom modifications of the initial therapeutic plan would be appropriate.(ABSTRACT TRUNCATED AT 400 WORDS)