Objective To compare the psychometric performance of the Dermatology Life Quality Index (DLQI-BRA) and Skindex-16 to assess quality of life (QoL) in Brazilian patients with dermatological diseases. Methods This was a cross-sectional study carried out in a dermatology outpatient clinic of the São Paulo State University, with 188 patients with dermatological diseases. QoL was evaluated using the Dermatology Life Quality Index (DLQI-BRA) and Skindex-16. Cronbach’s alpha and Intraclass Correlation for Perfect Concordance (ICC) were used to analyse the reliability and temporal stability, respectively. Results A positive correlation was found between the total Skindex-16 score and DLQI-BRA (0.75). Both instruments showed a significant (p< 0.01) reduction in their scores at the second assessment, demonstrating that they were sensitive in detecting changes in responsiveness in cases where there was a clinical change. Cronbach alpha coefficients for the instruments showed satisfactory performance (>0,7), but Skindex-16 displayed the highest Cronbach alpha (0.94; CI = 0.93–0.95). Conclusion Both instruments tested showed a good psychometric performance assessing QoL in patients with skin dermatoses. The instruments displayed reliability and temporal stability as well as responsiveness.