The relationships between worry and perceptions of likelihood and severity were evaluated across eight common diseases. Individual and disease variability in worry and perceptions were examined. 294 participants were recruited through the Multiplex Initiative, in which a genetic susceptibility test for eight common diseases was offered to healthy adults. Participants completed a baseline telephone survey and web-based surveys without a commitment to be tested, and then made a choice on testing. Between- and within-subjects analyses yielded the following main findings: (1) worry is more closely related to likelihood perceptions than to severity perceptions; (2) severity perceptions add significantly to explained worry variances above and beyond likelihood perceptions; (3) risk perceptions and worries form two clusters: cancer diseases and cardiovascular-metabolic diseases; and (4) variance in risk perception and worry is explained by a combination of between- and within-subjects variances. Risk perception research should attend to severity perceptions, within-subjects variability and inter-disease differences, and to strategies for grouping conditions.