OBJECTIVES: To compare the measurement precision and related properties between a short and generic instrument, 5-level EuroQoL Group’s 5-dimension (EQ-5D-5L) questionnaire, and a longer and disease-specific measure Functional Assessment of Cancer Therapy – Breast (FACT-B) questionnaire in assessing breast cancer patients. METHODS: This is an observational study of 269 Singaporean breast cancer patients. To compare discriminative ability cross-sectionally and longitudinally, the effect sizes (in standard deviation) of the EQ-5D-5L and the FACT-B in relation to various health indicators were estimated. Test-retest reliability was examined using the intraclass correlation (ICC) for patients with no change in self-assessed performance status or quality of life. For each non-inferiority assessment, a 90% confidence interval of the difference (FACT-B minus EQ-5D-5L) in effect size or ICC was estimated and compared with a pre-defined non-inferiority margin of 0.2. RESULTS: In a cross-sectional setting, the differences in the effect size favored EQ-5D-5L and the 90% confidence intervals totally fell within the zone that indicated the non-inferiority of the EQ-5D-5L (e.g. oncologist-assessed performance status: –0.26 to 0.04; patient-assessed performance status: –0.48 to –0.16; current evidence of disease: –0.28 to 0.08). In a longitudinal setting, the FACT-B showed larger effect sizes and ICCs than the EQ-5D-5L. The confidence intervals, however, overlapped the non-inferiority margin, thus non-inferiority in these two aspects could not be confirmed. CONCLUSIONS: The EQ-5D-5L was non-inferior to the FACT-B in discriminating breast cancer patients with different health conditions cross-sectionally. Its longitudinal measurement properties need further investigations. Depending on the specific research aims of studies, the EQ-5D-5L may serve as a reasonable alternative or supplementary instrument to the FACT-B in assessing breast cancer patients’ health outcomes.