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To examine symptom occurrence and severity and overall health-related quality of life (HRQOL) in patients receiving cancer therapy guided by genomic profiling (matched therapy) and patients receiving nonmatched therapy.A retrospective and secondary analysis of data from 129 individuals with breast or gynecologic cancer receiving care at a regional outpatient cancer center.Descriptive statistics and multiple linear regression analyses were performed. Study variables included symptom occurrence and severity, HRQOL, and person- and health-/illness-related factors. Symptom occurrence and severity were measured by the Therapy-Related Symptom Checklist (TRSC), and HRQOL was measured by the HRQOL-Linear Analogue Self-Assessment.Individuals receiving matched therapy had lower mean TRSC scores compared to individuals receiving nonmatched therapy, but the difference was not statistically significant. HRQOL scores among individuals receiving matched therapy were not significantly higher than those receiving nonmatched therapy. Individuals with higher TRSC scores had significantly lower HRQOL.The effects of matched therapy on an individual should be examined. Study findings are an initial step in understanding the symptom occurrence and severity and HRQOL.