BACKGROUND: A new HPV DNA chip test for the infection of 22 HPV genotypes was recently developed in Korea. This test using PCR and hybridization is inherently vulnerable to contamination, and to subjective qualitative test judgment. Hence, it warrants rigorous quality assurance measures. The authors would like to share operational experiences of the guidelines developed at Catholic University Holy Family Hospital. METHODS: Our quality assurance system of HPV DNA chip test comprised external quality controls, inter-laboratory proficiency tests, and internal quality controls. For the external quality controls, we analyzed the results of four years of participation in the quality assurance program by the Korean Laboratory Medicine Quality Assurance Association. The inter-laboratory proficiency tests with BioMedLab were done by single blind tests using patients' samples showing negative, single and multiple infections. The internal quality control dealt with methods to prevent contamination, and with reproduction tests. RESULTS: The results from the external quality control revealed consistency with HPV-16 in 7 trials during 4 years. The inter-laboratory proficiency tests showed a 82% consistency rate, 10 cases of inconsistency showing positive or negative mismatches, and 8 cases of genotypic mismatches. The 10 mismatches were due to the weak laser power of the scanner used in BioMedLab. The genotypic contamination rate found in the internal quality control was 3.3%, and the contamination by HPV-35 with low incidence rate was often observed. The contamination was not easily eliminated by re-tests from hybridization, but 80% of it was removed when re-tested with the remaining samples. The fluorescence intensity was not reproducible nor provide quantitative or semi-quantitative information. CONCLUSIONS: For quality assurance regarding HPV DNA chip tests, we suggest the following be implemented: technical quality control to rule out the false-negative and false-positive during PCR and hybridization; scanner quality control to prevent reading errors; and inter-laboratory proficiency tests.