Uncertainty in illness about diagnosis, symptoms, prognosis, treatments, and relationships with health professionals is a major psychosocial stressor for adolescents recently diagnosed with cancer. In this study, the theoretical linkages of the uncertainty in illness theory of perceived social support, uncertainty, and psychological distress were tested. Respondents consisted of 60 adolescents between the ages of 14 and 22 years who were recently diagnosed with cancer. Data were generated by three questionnaires and analyzed using Pearson product moment coefficients and multiple regressional analyses. Hypotheses tested were that among adolescents with cancer (1) there will be an inverse relationship between perceived social support and uncertainty; (2) there will be a positive relationship between uncertainty and psychological distress; (3) there will be an inverse relationship between perceived social support and psychological distress; and (4) there will be an inverse relationship between perceived social support and psychological distress when controlling for uncertainty. Findings were as follows: the first three hypotheses were supported; there was no relationship between perceived social support and psychological distress when controlling for uncertainty. An interaction effect of perceived social support and uncertainty explained 39% of the variance in psychological distress.