Background: The BestCyte® Cell Sorter Imaging System (BestCyte) facilitates algorithmic discrimination of clinically relevant cells in Pap test cytopathology by classifying and projecting images of cells in galleries based on cytomorphology. Warranted is awareness of potential BestCyte advantages as measured through 3 cytologists’ interobserver diagnostic concordance, specificity and sensitivity differentials, and equivalency grading relative to manual microscopy (MM). Objectives: Using 500 MM-reported ThinPrep thin-layers, analyze: (1) cytologists’ blinded BestCyte screening to raise Bethesda diagnoses; (2) correlate BestCyte and MM diagnoses (i.e., predicate) to establish Truth Reference Diagnoses (TRDx) from concordance between 4 possible diagnoses; (3) analyze cytologists’ and MM predicate diagnoses through 4 diagnostic thresholds defined by TRDx: NILM (Negative) for specificity, and ASCUS+, LSIL+, and ASCH+ (Positive) for graded sensitivity (with abnormal cells decreasing in size with increasing dysplasia); and, (4) statistically determine cytologists’ equivalency grading to MM using 95% Confidence Interval (CI) ranges. Results: 500 TRDx breakdown (n/%): NILM (241/48.2), ASCUS (79/15.8), ASCH (9/1.80), AGUS (2/0.40), LSIL (86/ 17.2), HSIL (68/13.6), CA (2/0.40), UNSAT (13/2.60). TRDx breakdown (n/%) per 4 of 4, 3 of 4, 2 of 4 diagnostic concordances: 264 (52.8%), 182 (36.4%), 54 (10.8%), respectively. No cases of discordant diagnoses were recorded. HSIL TRDx were established from 66.2% of 4 of 4 concordances, followed by NILM (59.3%), LSIL (46.5%), ASCUS (41.8%); antithetically, from 4.40% of 2 of 4 concordances. Specificity for MM predicate (NILM): 67.08%; for Cytologists 1, 2, and 3: 89.71%, 82.30%, 97.53%, respectively. For NILM threshold, cytologists revealed Significantly Superior equivalency to MM. Sensitivity for ASCUS+, LSIL+, and ASCH+ thresholds: MM (91.36%, 86.67%, 74.36%); Cytologist 1 (95.88%, 96.97%, 94.87%); Cytologist 2 (95.47%, 95.76%, 93.59%), Cytologist 3 (94.65%, 95.15%, 98.72%), respectively. Cytologists revealed Significantly Superior equivalency to MM for graded Positive thresholds; with Cytologist 3 for ASCUS+ being: Superior. Conclusions: BestCyte detects and efficiently displays abnormal cells in strategic galleries standardizing objectivity by systematizing mosaics of cell-types for cytologists’ consideration. BestCyte fosters consistent, enhanced cytologists’ sensitivity values for the ASCUS+, LSIL+, and ASCH+ Positive thresholds relative to MM. Also, BestCyte facilitates improved specificity and superior equivalency grading to MM reflecting efficient screening, and reduced labor. Confident interpretations of small dysplastic epithelial cells characteristic of HSIL led to exceptional interobserver diagnostic concordance inferring BestCyte is primed for effective cervical cancer screening practice. [ABSTRACT FROM AUTHOR]