1) Background: Studies indicate that caffeic acid (CA), caffeic acid phenethyl ester (CAPE) are compounds with potent chemopreventive effects. Breast cancer is a common cancer among women worldwide. The study shows comparison of caffeic acid and its ester activity in the cells of breast cancer line MDA-MB-231; 2) Methods: The cells of MDA-MB-231 were treated by CA and CAPE with doses from 10 to 100 µM in time 24 h and 48 h. Cytotoxicity MTT test, apoptosis by Annexin V and cell cycle with Dead Cell Assay were performed; 3) Results: The cytotoxic activity was greater for CAPE comparing to CA, in both incubation time (same dosage). IC50 values for CAPE were 27.84 (24h) and 15.83 (48h) and >10000 (24h) and >1000 (48h) for CA. Polyphenols induced apoptosis, higher apoptotic effect observed for CAPE (dose dependent). CAPE induced cell cycle arrest in S phase (time and dose dependent). Dose dependent decline G0/G1 phase (48h) and elimination of phase G2/M (100 µM of CAPE). For CA, only after 48 hours, small effect of cell cycle at phase S (however dose dependent), and slight decline of phase G0/G1 and G2/M only for highest doses (50 and 100 µM); 4) Conclusions: Comparing CA and CAPE activity, on the MDA-MB-231, we clearly see better activity of CAPE, with the same dosage and experiment time.