Background: We investigated pretreatment fasting glucose as a predictor of patients’ important outcomes in breast and colorectal cancers undergoing targeted therapies. Patients and methods: In a historic cohort of 202 breast and 218 colorectal cancers treated with targeted agents from 1998 to 2009, we used the Kaplan–Meier method and the log-rank test to estimate survival through tertiles of fasting glucose and the Cox proportional hazards model for multivariate analysis stratified by primary site of cancer and including gender, age and body mass index. Results: The median follow-up was 20 months (1–128). At 60 months, 65% of patients in the lowest tertile of fasting glucose did not experiment disease progression compared with 34% in the highest tertile (P= 0.001). Seventy-six percent of females in the lowest tertile showed no progression compared with 49% in the top tertiles (P= 0.015). In multivariate analysis, fasting glucose was a significant predictor of time to disease progression only in breast cancer patients in the first tertile compared with the third (P= 0.017). Conclusions: We found evidence of a predictive role of pretreatment fasting glucose in the development of resistance in breast cancer patients treated with targeted agents. Prospective studies are warranted to confirm our findings.