--- - |2+ Abstract Objective Identify which variables are predictors of treatment adherence in cancer patients. Methods Two hundred twenty cancer outpatients were evaluated by the following instruments: questionnaire on sociodemographic and clinical data, NEO‐FFI Personality Inventory Revised (NEO‐FFI‐R), Multidimensional Health Locus of Control (MHLC) scale, Hospital Anxiety and Depression Scale (HADS), patient's knowledge about cancer disease questionnaire, and Adherence Determinants Questionnaire (ADQ). A logistic regression analysis was applied to verify the predictive power of the variables, and network analyses were conducted through the qgraph package. Results The sample was composed of 138 (62.7%) women and 82 (37.3%) men. The mean age of participants was 54.66 (SD = 13.30), and the education level mean was 8.32 (DP = 3.76) years of study. Powerful others locus of control (LOC) and the personality factors conscientiousness and agreeableness are presented as predictors of high treatment adherence. The variable family cancer history, on the other hand, was a predictor of lower adherence levels. Conclusions The powerful others LOC may be connected with more trust and dependence in the health team, leading to better adherence. Specific characteristics of personality factors can help individuals to cooperate with their caregivers and to follow medical orders. The evaluated factors are interrelated and should be taken into account by health professionals when developing interventions to modify health‐related behaviors and treatment adherence. - Psycho-Oncology, EarlyView.