This review discusses the role of histological grade in breast cancer prognosis in the molecular era. Histological grade, based on the Nottingham Grading System (NGS), is a well-established prognostic factor that reflects tumor biological characteristics. It has been shown to provide important information about clinical behavior and is supported by genome-wide expression profiling studies. These studies suggest that molecular tests may replace histological grading as the 'gold standard' for prognosis and treatment response prediction. However, molecular tests must provide additional prognostic or predictive information beyond traditional factors. The NGS remains a simple, cost-effective method for assessing tumor biology and is essential for clinical decision-making. It is particularly useful in defining treatment options for patients with ER-positive, LN-negative or low-volume LN metastatic disease. While molecular tests like Oncotype DX and MammaPrint have shown promise, they are not yet widely available in all regions. Histological grading, when performed properly, remains a reliable and cost-effective alternative for assessing tumor biology and patient prognosis. The review emphasizes the importance of histological grade in breast cancer staging and treatment algorithms, and highlights the need for continued research to evaluate the role of molecular tests in conjunction with histological grading. The consensus is that histological grade should be incorporated into staging systems and algorithms to define therapy for breast cancer patients.This review discusses the role of histological grade in breast cancer prognosis in the molecular era. Histological grade, based on the Nottingham Grading System (NGS), is a well-established prognostic factor that reflects tumor biological characteristics. It has been shown to provide important information about clinical behavior and is supported by genome-wide expression profiling studies. These studies suggest that molecular tests may replace histological grading as the 'gold standard' for prognosis and treatment response prediction. However, molecular tests must provide additional prognostic or predictive information beyond traditional factors. The NGS remains a simple, cost-effective method for assessing tumor biology and is essential for clinical decision-making. It is particularly useful in defining treatment options for patients with ER-positive, LN-negative or low-volume LN metastatic disease. While molecular tests like Oncotype DX and MammaPrint have shown promise, they are not yet widely available in all regions. Histological grading, when performed properly, remains a reliable and cost-effective alternative for assessing tumor biology and patient prognosis. The review emphasizes the importance of histological grade in breast cancer staging and treatment algorithms, and highlights the need for continued research to evaluate the role of molecular tests in conjunction with histological grading. The consensus is that histological grade should be incorporated into staging systems and algorithms to define therapy for breast cancer patients.