Background: Patients with muscle-invasive bladder cancer (MIBC) that underwent neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC) show improved overall survival. Those with a pathological complete response (pCR) usually have the best prognosis. In the literature, improved response to NAC has been associated with basal tumor characteristics in MIBC so far. The aim of the present study was to examine the association of luminal (KRT20) and basal (KRT5) mRNA expression patterns at transurethral resection (TUR) with pCR at RC after NAC in a contemporary cohort of consecutive MIBC patients. Methods: Clinical Data and formalin fixed paraffin embedded tumor tissue samples from TUR and RC of 49 patients with MIBC were retrospectively analyzed. Using RT-PCR KRT20 and KRT5 mRNA expression were measured in 40-∆Ct values and normalized against the control gene CALM2. Statistical analyses comprised nonparametric and chi² testing, partition models and spearman correlation analyses. Results: The study cohort had a median age of 63 years and consisted of 38/49 (78%) males. After NAC, 17/49 (35%) patients had cPR. Using partition models, we found that patients with high-KRT20 (≥39.5 ∆C_t) had a higher chance of pCR (57% vs. 26%, p=0.04). Using a cutoff for KRT5 at <38.1 ∆C_t within the subgroup of patients with low-KRT20 (<39.5 ∆C_t, n=35), we found poorest response among low-KRT20/low-KRT5 compared to low-KRT20/high-KRT5 and high-KRT20 (13% vs. 37% vs. 57%, p=0.29), respectively. For low-KRT20/low-KRT5, low-KRT20/high-KRT5 and high-KRT20 median KRT5 was 34.8 vs. 39.5 vs. 34.1 ∆C_t (p=0.001) and median KRT20 was 37.9 vs. 32.9 vs. 40.1 ∆C_t,(p=0.001), respectively. Conclusions: Patients with MIBC showing high expression of KRT20 were more likely to show pCR at RC after NAC. Moreover, we were able to identify a high risk group of patients with lowKRT20/lowKRT5 that was less likely to achieve pCR at RC after NAC. Our findings are contradicting previous studies and need further verification in larger cohorts. However, our results might be useful for treatment stratification in MIBC patients.