Abstract Purpose To investigate the relationship between fluorescein breakup patterns (FBUPs) and clinical manifestations in dry-eye cases. Design Cross-sectional study. Methods In 106 eyes of 106 subjects (19 males, 87 females; mean age: 64.2 years), FBUPs were categorized into 1 of the following 5 break (B) types: area (AB, n=19); spot (SB, n=22); line (LB, n=24); dimple (DB, n=19); random (RB, n=22 eyes), and dry-eye-related symptoms using the visual analog scale (VAS, 100mm=maximum), tear meniscus radius (TMR, mm), tear-film lipid-layer interference grade (IG) (grades 1-5; 1=best) and spread grade (SG) (grades 1-4; 1=best), tear-film non-invasive breakup time (NIBUT, seconds), FBU time (FBUT, seconds), corneal-epithelial damage (CED) score (15 points=maximum), ocular-surface epithelial damage (OSED) score (9 points=maximum), and the Schirmer 1 test (ST1, mm) were examined and compared between each FBUP. Results In each FBUP, eye dryness and fatigue were the severest symptoms. Characteristic symptoms were sensitivity to light, heavy eyelids, pain, foreign-body sensation, difficulty opening the eye, and discharge for AB, heavy eyelids for SB, foreign-body sensation for LB. Statistically significant differences were found in TMR (AB-SB, -DB and -RB; LB-RB), IG (AB-all other FBUP; LB-SB and -DB), and SG (AB-all other FBUPs), FBUT (AB-LB, -DB, and –RB; SB-DB and –RB; LB-RB; DB-RB), and NIBUT (AB-all other FBUPs; SB-DB and-RB, and LB-RB), CED (AB-all other FBUPs; LB-SB, -DB, and -RB) and OSED (AB-SB, -LB, and -DB; LB-SB, -DB, and -RB), and ST1 (AB-SB, -DB, and -LB) (p<0.05 in each comparison). Conclusions The 5 different FBUPs constituted different groups, reflecting different pathophysiologies.