AIM This study was a retrospective analysis of our experience with severe cross-hypersensitivity reactions (HSR) to the taxanes paclitaxel (P) and docetaxel (D) in patients with breast cancer. PATIENTS AND METHODS We evaluated patients with breast cancer treated with P or D who experienced severe HSR to one of the two taxanes. Severe HSR was defined as any reaction severe enough to warrant discontinuation of the drug. Initial intravenous premedication for paclitaxel was dexamethasone (20 mg), ranitidine (50 mg) and dexchlorpheniramine (10 mg). For docetaxel, dexamethasone (4 mg) orally every 12 hours was administered the day before infusion and dexamethasone (20 mg) was administered intravenously prior to infusion. After severe HSR to the taxane and 30 minutes before infusion of another taxane, we administered dexamethasone (20 mg), ranitidine (50 mg) and dexchlorpheniramine (10 mg) iv as a premedication, and we also increased the time of the infusion. RESULTS Between March 2009 and April 2010, 23 patients experienced an initial severe HSR to taxane (12 P, 11 D). Substitution of another taxane was conducted in 17 patients in the two weeks following the initial HSR. Eight patients had an initial HSR with P, and three had a cross-HSR to D. Nine patients had an initial HSR to D, and four of these patients had a cross-HSR to P. Among the 17 patients who received both taxanes, 7 (41%) had a cross-HSR. All cross- HSRs were sufficiently severe (grade 3-4) to suspend taxane treatment permanently. In the remaining 6 patients, a desensitisation protocol to taxanes was performed by increasing the dose of the diluted drug (4 P, 2 D), which resulted in administration of the drug without complications in all cases. There were no treatment-related deaths. CONCLUSION Severe cross-HSR between P and D occurred in a significant proportion of our patients with breast cancer, so care must be taken when substituting taxanes (paclitaxel and docetaxel). A desensitisation protocol can be an effective alternative to decrease the risk of a new HSR.