We present a polyclonal outbreak of vancomycin-resistant enterococci (VRE) colonization in a pediatric oncology department and the role of a bundle of actions. After the occurrence of VRE bloodstream infections in 2 patients, an active surveillance of VRE colonization was started. Enhanced infection control measures and closure of the department to new admissions for the first 3 months were implemented. Among 32 patients screened for VRE, 21 were found colonized. Daily prevalence of VRE colonization among hospitalized patients ranged from 40% to 75%, but no new VRE infections occurred. Monthly incidence of VRE colonization decreased from 2.5 to 0.6 cases per 100 occupied bed-days at the end of this outbreak by the implementation of the above-mentioned measures. All VRE isolates tested were Enterococcus faecium carrying VanA gene. Pulsed field gel electrophoresis showed a polyclonal outbreak. A case-control study did not show any particular risk factors for colonization. High use of glycopeptide was noted before study outbreak that was drastically decreased during the study but only temporarily. Control of VRE in pediatric oncology departments with high colonization rates is challenging and requires a multifaceted strategy. Polyclonal spread of VRE found in this study suggests a possible effect of prior antimicrobial overuse and the critical need for antimicrobial stewardship especially in the era of multidrug-resistant bacteria.