Purpose: 3–8% of US adults with cancer are enrolled in a clinical trial due to various barriers to enrollment. The purpose of this study is to evaluate the variability of eligibility criteria, which currently have no standard guidelines. Methods: This descriptive analysis utilized all therapeutic breast protocols offered at the University of Alabama at Birmingham between 2004 and 2020. Exclusion criteria were abstracted using OnCore and ClinicalTrials.gov. Laboratory values included liver function tests and hematologic labs. Comorbid conditions included congestive heart failure, cardiovascular disease, central nervous system (CNS) metastases, and prior cancer history. Comorbid conditions were further analyzed by amount of time protocols required participants to be from diagnosis or exacerbation-free. Results: 102 protocols were eligible. Among liver laboratory values, bilirubin (78%) was included in most protocols ranging from institutional upper limit of normal (ULN) (9%) to 3xULN (2%), with 1.5xULN (56%) being most common. Similar variability was observed in alanine transaminase and aspartate transaminase. Among hematological labs, 82% of protocols defined a lower limit of acceptable absolute neutrophil count ranging from 500 μL (1%) to 1800 μL (1%), with 1500 μL (64%) being most common. Of the comorbid conditions, exclusion criteria varied for congestive heart failure (49%), an acute exacerbation of cardiovascular disease (80%), CNS metastases (59%), and a prior cancer (66%). The allowable timeframe varied between protocols for cardiovascular disease and prior cancer. Conclusion: Substantial heterogeneity was observed across laboratory values and comorbid variables among protocols. Future research should focus on defining standardized eligibility criteria while allowing for deviation based on drug specificity.