Background: The cultural adaptation of quality of life instruments and their psychometric evaluation should be done rigorously and according to the standards. Objective: This study assessed the reliability and construct validity of the Colombian version of the Skindex-29 instrument. Methods: Patients with inflammatory or generalized skin diseases and with non-inflammatory or localized diseases, and healthy individuals were included. We determined the intra- and inter-observer reliability. Results: We surveyed 265 individuals. Cronbach's alpha was 0.957 for the total instrument. The intraclass correlation coefficients for intra-observer and inter-observer consistency were higher than 0.9. Patients with generalized or inflammatory diseases had higher scores than those with non-inflammatory or isolated lesions. Conclusions: The results support the construct validity of the studied instrument. In the future, it is necessary to evaluate other psychometric properties such as its content and criteria validity, and its sensitivity to change.