The results showed that higher expression of SPAG5 was associated with worse RFS (n = 3557, HR = 1.72, 95% CI 1.54–1.94, p < 0.001), OS (n = 1117, HR = 1.86, 95% CI 1.46–2.37, p < 0.001), and DMFS (n = 1610, HR = 1.88, 95% CI 1.53–2.32, p < 0.001) in patients with breast cancer. Here, SPAG5 is linked to breast cancer.