Context: Breast development is a key feature of feminization and therefore important to transwomen (male-to-female transgender persons). It is not exactly known when breast development starts after initiating cross-sex hormone therapy (CHT) and how much growth may be expected. Objective: To investigate breast development in transwomen during their first year of CHT and whether clinical or laboratory parameters predict breast development. Design: This study was performed as part of the European Network for the Investigation of Gender Incongruence, which is a prospective multicenter cohort study. Setting: Gender clinics in Amsterdam, Ghent, and Florence. Participants: Transwomen who completed the first year of CHT (n = 229). Intervention: CHT. Main Outcome Measures: Breast development in centimeter and cup size. Results: The median age of the included transwomen was 28 years (range, 18 to 69). Mean breast-chest difference increased to 7.9 +/- 3.1 cm after 1 year of CHT, mainly resulting in less than an AAA cup size (48.7%). Main breast development occurred in the first 6 months of therapy. Serum estradiol levels did not predict breast development after 1 year of CHT (first quartile, 3.6 cm [95% confidence interval (CI), 2.7 to 4.5], second quartile, 3.2 cm [95% CI, 2.3 to 4.2], third quartile, 4.4 cm [95% CI, 3.5 to 5.3], and fourth quartile, 3.6 cm [95% CI, 2.7 to 4.5]). Conclusion: This study shows that, after 1 year of CHT, breast development is modest and occurs primarily in the first 6 months. No clinical or laboratory parameters were found that predict breast development.