Abstract: The traditional classification of pituitary neuroendocrine tumors (PitNETs) based on hormone types and clinical manifestations has limitations and often leads to diagnostic confusion. In recent years, a molecular classification centered on key transcription factors—pituitary-specific POU-class homeodomain transcription factor 1 (PIT1), T-box transcription factor 19 (TBX19, also known as TPIT), and steroidogenic factor 1 (SF1)—has been established by the World Health Organization (WHO) as the gold standard for lineage classification due to its superior diagnostic efficacy. This classification strategy effectively overcomes the limitations of traditional hormonal immunohistochemistry, significantly reduces the misdiagnosis of "null cell adenomas, " and improves the assessment of tumor invasiveness. Its core value lies in achieving precise molecular tracing of tumor cell origins through lineage-specific transcription factors: PIT1 regulates the GH/PRL/TSH lineage, TPIT governs the ACTH lineage, and SF1 marks the FSH/LH lineage. This classification system innovatively identifies high-risk subtypes such as immature PIT1-lineage tumors and silent corticotroph adenomas, and explicitly defines "null cell tumors" as those negative for multiple transcription factors and all pituitary-related hormones. Furthermore, the expression patterns of these transcription factors are closely associated with tumor biological behaviors, including invasiveness, drug sensitivity, and recurrence tendency, providing critical molecular evidence for prognostic stratification, targeted therapy, and individualized surgical planning. This review aims to systematically summarize recent advances in the role of transcription factors in PitNET classification, discuss their mechanisms of action and clinical application prospects, and offer new insights for enhancing the precision of diagnosis and treatment of PitNETs.