Results from multinational clinical trials are globally adopted into the routine clinical practice in most countries. Changes in the natural history and incidence of certain diseases as well as in drugs toxicities related to yearly seasons have been reported, however, variations related to climate have never been described. In our study, we assessed whether yearly seasons and climate could influence the chemotherapy toxicity profile. We analyzed the toxicities recorded in the phase III GEICAM 9906 study which was run in different geographically and climatically/seasonally regions in Spain. In this trial 1246 patients were randomized and eligible to receive FEC90 ×6 cycles or FEC90 ×4 cycles followed by eight doses of weekly paclitaxel (T). The results showed differences in hematological and non-hematological toxicities in relation to the season of the year and the climate of the area in which the treatment was administered. We found a higher hematological toxicity in warm seasons (spring and summer) and in Oceanic climate regions (Neutropenia G4: 7.8 vs. 1.0 vs. 1.0%, P < 0.0001). Asthenia was greater frequency in the summer period (FEC90: 21.1%, T: 15.3%) as well as in the Mediterranean areas (FEC: 28% T: 27.2%). Also we observed liver transaminase elevations were more frequent in the summer and in the Oceanic areas. Myalgias and secondary sensory neuropathy to paclitaxel were recorded more frequently during autumn. Climate should be considered a significant variable in toxicity to chemotherapy.