Objective: We aimed to explore the factors involved in high-grade squamous intraepithelial lesion (HSIL) or more severe lesions undetected by colposcopy-directed biopsy (CDB). Materials and Methods: We retrospectively reviewed 2,427 patients diagnosed with low-grade squamous intraepithelial lesion (LSIL) by CDB. After undergoing the loop electrosurgical excision procedure (LEEP), 2,023 patients were classified as having LSIL (group A), 393 as having HSIL (group B), 6 as having squamous cell carcinoma (group C), and 5 as having adenocarcinoma in situ and adenocarcinoma (group D). Results: The patients in groups D (47.6 ± 4.0) and B (39.7 ± 8.2) were significantly older (p < 0.01) than those in group A (37.6 ± 8.4). The proportion of multicentricity detected by CDB was significantly higher in group B (13.2%) than in group A (8.6%) (p = 0.003). CDB detected glandular involvement (GI) in 0.35% of the patients in group A, 0.51% in group B, and none in groups C and D (p = 0.964). The circumference, width, and length of LEEP specimens were significantly higher (p = 0.000, p = 0.011, and p = 0.000, respectively) in group B (2.8 ± 0.8 cm, 0.75 ± 0.24 cm, and 1.23 ± 0.29 cm, respectively) than in group A (2.6 ± 0.9 cm, 0.72 ± 0.23 cm, and 1.13 ± 0.31 cm, respectively), which are indicative of the presence of larger lesions in group B. Conclusion: Older age, but not GI, in patients diagnosed with LSIL by CDB is indicative of HSIL+ lesions. CDB-diagnosed LSIL patients with large lesion sizes and multicentric lesions may have occult HSIL.