Prostaglandins (PGs) play extensive regulatory roles in physiological processes such as reproductive development, homeostasis regulation, and tissue regeneration in vertebrates, yet their distribution and functions in invertebrates remain poorly characterized. To address this knowledge gap, this study established a quantitative analytical method targeting prostaglandin E₂ (PGE₂) and prostaglandin D₂ (PGD₂) in multiple tissues of bivalves using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with multiple reaction monitoring (MRM), employing the potential model bivalve dwarf surf clam (Mulinia lateralis) as the experimental organism. Through dual validation of characteristic fragment ions and retention time, we systematically identified the distribution profiles of PGE₂ and PGD₂ in six major tissues of M. lateralis: both PGs were detected in the mantle, gill, gonad, and digestive gland. Quantitative analysis, based on external standard calibration curves, revealed that PGE₂ concentrations were consistently higher than PGD₂ across all examined tissues. Notably, the gill and mantle emerged as the primary accumulation sites for PGs, with their combined PGE₂ and PGD₂ content contributing to 82.14% of the total. Further analysis demonstrated that fast-growing individuals exhibited significantly higher PGE₂ and PGD₂ levels than in slow-growing counterparts (increased by 24.51% and 61.11%, respectively; P < 0.01), suggesting potential involvement of PGs as key regulatory factors in the growth modulation of M. lateralis. This study provides initial insights into the tissue-specific distribution of PGs and their potential association with growth rate in M. lateralis, generating fundamental evidence for investigating growth regulation mechanisms and genetic improvement practices in bivalves.