Background <p>The long noncoding RNA (lncRNA) FAM83H-AS1 plays a critical role in the development and progression of various cancers. This study evaluates the feasibility of serum FAM83H-AS1 as a diagnostic and staging marker for ovarian cancer (OC), addressing its previously unclear diagnostic value.</p> Methods <p>Our study included 118 patients diagnosed with OC, 73 individuals with benign ovarian disease (BOD), and 61 healthy controls (HCs). The expression of serum FAM83H-AS1 was quantified via RNA extraction followed by RT-qPCR. The levels of CA125 and HE4 were detected via a chemiluminescence microparticle immunoassay, and the risk of ovarian malignancy algorithm (ROMA) was calculated. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic effect of FAM83H-AS1. Univariate and multivariate Cox regression analyses were employed to identify independent prognostic factors, while Kaplan–Meier analysis with the log-rank test was used to compare survival differences.</p> Results <p>The levels of FAM83H-AS1 were significantly elevated in OC patients compared with those in individuals with BOD and HCs (<i>P</i> &lt; 0.001). Additionally, FAM83H-AS1 expression levels were markedly higher in advanced TNM stages and in cases of metastasis. ROC curve analysis demonstrated robust diagnostic performance for FAM83H-AS1 alone (AUC = 0.824), and the combined FAM83H-AS1 + ROMA panel achieved superior accuracy (AUC = 0.909). Stepwise multivariate analysis identified FAM83H-AS1 as an independent diagnostic predictor for OC. A unit increase in this marker was associated with a 6.9% increase in the odds of OC (<i>P</i> = 0.030). FAM83H-AS1 levels were positively correlated with TNM stage, lymphatic metastasis, distal metastasis, peritoneal metastasis, and established biomarkers (CA125, HE4, and ROMA; <i>P</i> &lt; 0.05). Notably, postoperative FAM83H-AS1 levels were significantly lower in 22 paired patients (<i>P</i> &lt; 0.01), confirming its tumor-derived origin. Survival analysis indicated that elevated serum levels of FAM83H-AS1 expression serve as an independent prognostic factor associated with decreased progression-free survival (PFS) (HR = 8.251, <i>P</i> = 0.041). However, it failed to exhibit independent prognostic significance for overall survival (OS), as the correlation with OS observed in the univariate analysis was rendered non-significant in the multivariate analysis after adjusting for TNM stage. Kaplan-Meier curves further validated significantly worse survival outcomes for patients categorized in the high-expression group (<i>P</i> &lt; 0.05).</p> Conclusions <p>This research is the first to indicate that serum FAM83H-AS1 may serve as a novel noninvasive biomarker for the diagnosis of OC. The combination of FAM83H-AS1 and ROMA demonstrated excellent diagnostic efficacy. Serum FAM83H-AS1 is promising for monitoring the stage and progression of OC patients.</p>