The prognosis of patients with colorectal liver metastases (LMs) is mostly established on clinical variables or on the anatomic extent of colorectal cancer (CRC). Histopathological factors of LMs which may actually reflect the biological aggressiveness of the tumor are not routinely considered to define the risk of worse clinical outcome in those patients. The number of poorly differentiated clusters (PDCs) of neoplastic cells in primary CRC is associated with metastatic risk and bad prognosis, but PDC presence in LMs has been barely analyzed thus far. We assessed PDC presence in the histological slides of surgically resected and synchronous LMs in 63 patients with CRC who had been not submitted to any neoadjuvant treatments. Then, we analyzed its association with patients’ cancer-specific survival (CSS) or progression-free survival. The presence of PDCs (P = .016) and PDC localization at tumor edge of LMs (P = .0004) were significantly associated with shorter CSS. PDC presence at the periphery of LMs and positive resection margin were independent prognostic variables for CSS. PDC localization at the tumor edge of LMs was a significant (P = .0079) and independent prognosticator of shorter progression-free survival. Our data suggest that PDC presence and peripheral localization in LMs may be relevant to predict outcome and useful for clinical decision making in patients with colorectal synchronous LMs. •The prognosis of patients with colorectal LM is commonly established on clinical features.•Low attention is given to histopathological features of LM as prognostic factors.•The number of PDCs in primary CRC is correlated with prognosis and metastatic disease.•This study shows that PDC presence and peripheral localization in synchronous colorectal LMs are associated with bad prognosis.•Assessment of PDC counting in synchronous LMs may be useful to assess prognosis and for clinical decision making in patients with stage IV CRC.