The aim of this study was to investigate the expression of thyroid hormone receptor β1 (THRβ1) by immunohistochemistry in breast cancer (BC) tissues and to correlate the results with clinico-biological parameters. In a well-characterized cohort of 274 primary BC patients, THRβ1 was widely expressed with a predominant nuclear location, although cytoplasmic staining was also frequently observed. Both nuclear and cytoplasmic THRβ1 were correlated with high-risk BC markers such as human epidermal growth factor receptor 2 (HER2), Ki67 (also known as MKI67), prominin-1 (CD133), and N-cadherin. Overall survival analysis demonstrated that cytoplasmic THRβ1 was correlated with favourable survival ( = 0.015), whereas nuclear THRβ1 had a statistically significant correlation with poor outcome ( = 0.038). Interestingly, in our cohort, nuclear and cytoplasmic THRβ1 appeared to be independent markers either for poor ( = 0.0004) or for good ( = 0.048) prognosis, respectively. Altogether, these data indicate that the subcellular expression of THRβ1 may play an important role in oncogenesis. Moreover, the expression of nuclear THRβ1 is a negative outcome marker, which may help to identify high-risk BC subgroups.