BACKGROUND: Creatine supplementation is an effective ergogenic nutrient for athletes, as well as for people starting a health or fitness program. Resistance training has previously been identified as an important method of increasing muscle mass and strength, especially in people with cancer to avoid sarcopenia. The potential of creatine supplementation for adaptations produced by resistance training in patients with cancer is still unknown. The primary aim of this study is to evaluate the effectiveness of a supervised resistance training program intervention with and without creatine supplementation in patients with breast cancer. METHODS: Is a multicentre, randomized, blind, placebo-controlled study. Patients will be randomly assigned to a control group and 2 experimental groups. The first training resistance group (RG) will perform resistance training, while the second experimental resistance-creatine group will perform the same resistance training as the RG and will also receive a 5 g/d creatine supplementation during the intervention. RG participants will follow the same daily dosing protocol, but in their case, with dextrose/maltodextrin. Resistance training will be a 16-week supervised workout that will consist of a series of resistance exercises (leg press, knee extension, knee bends, chest press, sit-ups, back extensions, pull-ups, and shoulder press) that involve the largest muscle groups, performed 3 times a week on nonconsecutive days. Both the RG and the resistance-creatine group will receive a supplement of soluble protein powder (20 to 30 g) daily. CONCLUSION: This intervention will help to better understand the potential of nonpharmacological treatment for improving strength and well-being values in patients with breast cancer with and without creatine supplementation.