Purpose: The aim of this study was to estimate the minimal clinical important difference (MCID) of the World Health Organization Quality of Life assessment instrument (WHOQOL-100) for women with early-stage breast cancer. If the MCID is known, then the instrument is also useful for individual patients and thus useful in clinical practice. In this study, the MCID is the smallest change in quality of life (QOL) scores considered clinically relevant for patients. Methods: Data were derived from a prospective study in which 223 women with early-stage breast cancer and 383 women with benign breast problems completed the WHOQOL-100. MCID values were determined by two distribution-based methods (0.5 standard deviation (SD) and 1 standard error of measurement (SEM)) and an anchor-based method. Results: For 0.5 SD, MCID estimates ranged from 0.64 to 0.94, and for 1 SEM, MCID estimates ranged from 0.69 to 1.18. The anchor-based approach resulted in MCID estimates ranging from -1.56 to -0.71 for decline and from 0.51 to 1.27 for improvement. Conclusion: A change in score of 1 on the WHOQOL-100 is proposed as the MCID for women with early-stage breast cancer. 2012 Springer-Verlag Berlin Heidelberg.