Nucleated red blood cells (NRBCs) are premature erythrocyte precursors that reside in the bone marrow of humans of all ages as an element of erythropoiesis. They rarely present in healthy adults’ circulatory systems but can be found circulating in fetuses and neonates. An NRBC count is a cost-effective laboratory test that is currently rarely used in everyday clinical practice; it is mostly used in the diagnosis of hematological diseases/disorders relating to erythropoiesis, anemia, or hemolysis. However, according to several studies, it may be used as a biomarker in the diagnosis and clinical outcome prognosis of preterm infants or severely ill adult patients. This would allow for a quick diagnosis of life-threatening conditions and the prediction of a possible change in a patient’s condition, especially in relation to patients in the intensive care unit. In this review, we sought to summarize the possible use of NRBCs as a prognostic marker in various disease entities. Research into the evaluation of the NRBCs in the pediatric population most often concerns neonatal hypoxia, the occurrence and consequences of asphyxia, and overall neonatal mortality. Among adults, NRBCs can be used to predict changes in clinical condition and mortality in critically ill patients, including those with sepsis, trauma, ARDS, acute pancreatitis, or severe cardiovascular disease.