BRIP1 has been implicated in hereditary breast cancer due to its role in DNA repair and cell-cycle control. BRIP1 was first associated with breast cancer in 2006, when a study of 1,212 familial breast cancer cases and 2,081 controls reported a significant two-fold increased risk. Many commercial laboratories include this gene on breast cancer susceptibility genetic panels. Now, in a large collaborative study (comprising more 100,000 tested persons), Easton and colleagues report no evidence of an association between BRIP1 truncating mutations and breast cancer risk. This suggests that BRIP1 is not a breast cancer susceptibility gene and highlights the need to use caution when interpreting the results of initial association studies particularly for rare variants with modest effects. (By Victoria Sopik and William Foulkes, http://jmg.bmj.com/content/early/2016/02/26/jmedgenet-2015-103648 )