The objective of this study was to determine the prevalence of significant lesions defined as high gradesquamous intraepithelial lesions (HSIL), adenocarcinoma in situ (AIS) and invasive carcinoma in women whohad HPV-positive and cytology negative co-testing screening results. This retrospective study was conducted inChiang Mai University Hospital between May, 2013 and August, 2014. Hybrid capture 2 (HC2) was used forHPV testing and conventional Pap smears for cytologic screening. A repeat liquid-based cytology (LBC) wasperformed in women with such co-testing results followed by colposcopy. Random biopsy was performed in casesof normal colposcopic findings. Further investigations were carried out according to the biopsy or the repeatLBC results. During the study period, 273 women met the criteria and participated in the study. The mean ageof these women was 46.4 years with 30% of them reporting more than one partner. The median interval time tocolposcopy was 165 days. About 40% showed an abnormality in the repeat cytology. Significant cervical lesionswere found in 20 (7.3%) women, including 2 invasive cancers. Of interest was that only 2 of 20 significant lesionswere diagnosed by colposcopic examination while the remainder were initially detected by cervical biopsy andabnormal repeat cytology. In conclusion, the prevalence of significant cervical lesions in HPV positive andcytology negative women in Northern Thailand was 7.3%. Further diagnostic work up with repeat cytologyfollow by colposcopy is recommended. Random biopsy should be performed even when the colposcopic findingsare normal.