Medical professionals are increasingly expected to deliver genetic services in daily patient care. However, genetics education is considered to be suboptimal and in urgent need of revision and innovation. We designed a Genetics e-learning Continuing Professional Development (CPD) module aimed at improving general practitioners' (GPs') knowledge about oncogenetics, and we conducted a randomized controlled trial to evaluate the outcomes at the first two levels of the Kirkpatrick framework (satisfaction, learning and behavior). Between September 2011 and March 2012, a parallel-group, pre-and post-retention (6-month follow-up) controlled group intervention trial was conducted, with repeated measurements using validated questionnaires. Eighty Dutch GP volunteers were randomly assigned to the intervention or the control group. Satisfaction with the module was high, with the three item's scores in the range 4.1-4.3 (5-point scale) and a global score of 7.9 (10-point scale). Knowledge gains post test and at retention test were 0.055 (P<0.05) and 0.079 (P<0.01), respectively, with moderate effect sizes (0.27 and 0.31, respectively). The participants appreciated applicability in daily practice of knowledge aspects (item scores 3.3-3.8, five-point scale), but scores on self-reported identification of disease, referral to a specialist and knowledge about the possibilities/ limitations of genetic testing were near neutral (2.7-2.8, five-point scale). The Genetics e-learning CPD module proved to be a feasible, satisfactory and clinically applicable method to improve oncogenetics knowledge. The educational effects can inform further development of online genetics modules aimed at improving physicians' genetics knowledge and could potentially be relevant internationally and across a wider range of potential audiences.