Background: Breast cancer is the leading cause of cancer-related mortality among women worldwide. Platelet indices and serum iron have been implicated in cancer pathophysiology and may serve as potential biomarkers in breast cancer. Objective: This study aimed to evaluate the levels of platelet indices and serum iron in breast cancer patients attending Imo Specialist Hospital, Owerri, Nigeria. Methods: A total of 60 subjects, comprising 30 breast cancer patients and 30 apparently healthy controls, were recruited for this cross-sectional study. Ethical approval was obtained, and informed consent was secured from all participants. Structured questionnaires were administered to gather socio-demographic and clinical data. Six (6) mL of venous blood was collected from each participant; 2mL was dispensed into ethylenediaminetetraacetic acid (EDTA) containers for platelet indices determination using an autoanalyzer, and 4 mL into plain tubes for serum separation and iron analysis using spectrophotometry. Data was analyzed using SPSS version 27, with mean, standard deviation, Student's t-test, Pearson correlation, and p-values determined. Results: The mean values of mean platelet volume (MPV), platelet distribution width (PDW), and serum iron were significantly higher in breast cancer patients [(10.51±1.89) fL, (20.29±7.66) %, and (50.40±15.22) µg/dL, respectively] compared to controls [(7.81±0.46) fL, (15.33±2.89) %, and (27.13±8.45) µg/dL] with p-values of 0.000, 0.002, and 0.000, respectively. However, no significant differences were observed in plateletcrit (PCT) (0.23±0.23) % and platelet large cell ratio (P-LCR) (22.91±7.52) % in breast cancer patients when compared to controls (0.19±0.07) % and (17.59±20.09) % (p=0.338 and p=0.180]. Age-stratified analysis revealed no significant differences in MPV, PDW, PCT, P-LCR, and serum iron between breast cancer patients aged 35–50 years and those older than 50 years (p>0.05). Furthermore, there was a non-significant positive correlation between serum iron and platelet indices, including MPV (r=0.09, p=0.607), PDW (r=0.04, p=0.833), PCT (r=0.15, p=0.421), and P-LCR (r=0.19, p=0.304). Conclusion: This study shows that breast cancer is associated with significantly raised MPV, PDW, and serum iron levels, suggesting enhanced platelet activation and altered iron metabolism in affected patients. These findings imply that MPV and PDW may serve as useful markers for platelet activation, tumor progression, and inflammation in breast cancer. Additionally, elevated serum iron may reflect its involvement in breast cancer pathogenesis. Routine evaluation of platelet indices, particularly MPV and PDW, along with serum iron levels, should be recommended as part of the diagnostic and prognostic assessment of breast cancer patients. Further large-scale studies are warranted to validate the utility of these parameters as biomarkers for breast cancer progression and therapeutic monitoring.