BackgroundAccurate　identification　of　small　metastatic　lymph　nodes　(LNs)　remains　a　significant　challenge　with　conventional　ultrasound　(US)　due　to　its　limitations　in　sensitivity　for　smaller　LNs.　The　use　of　contrast-enhanced　ultrasound　(CEUS),　especially　with　perfluorobutane　in　the　postvascular　phase　of　CEUS,　may　improve　the　diagnosis　of　metastatic　LNs　in　cancer　patients.　We　sought　to　investigate　the　diagnostic　accuracy　of　the　postvascular　phase　of　CEUS　with　perfluorobutane　in　identifying　suspected　small　cervical　LNs　in　cancer　patients.　MethodsThis　prospective　study　enrolled　consecutive　cancer　patients　with　small　cervical　LNs　suspected　to　be　malignant　on　US　from　May　2023　to　January　2024.　All　patients　underwent　CEUS　with　perfluorobutane　injection,　followed　by　observation　during　the　vascular　(6-60　s)　and　postvascular　(10-30　min)　phases　before　biopsy.　The　reference　standard　was　histological　assessment　of　the　LNs　through　biopsy.　The　US　and　CEUS　features　were　analyzed　to　assess　the　diagnostic　performance　of　the　US,　vascular　phase-CEUS,　and　postvascular　phase-CEUS　features,　as　well　as　their　association　with　LN　size.　ResultsThe　final　dataset　included　229　participants　(mean　age,　57　years　+/-　11　[SD]　[range,　28-80];　121　women)　with　229　suspected　LNs,　including　125　metastatic　and　104　benign　LNs.　Hypo-enhancement　or　no　enhancement　in　the　postvascular　phase　of　CEUS　show　excellent　sensitivity　(97%)　and　a　high　negative　predictive　value　(93%).　The　area　under　the　receiver　operating　characteristic　(ROC)　curve　of　postvascular　phase-CEUS　is　0.763,　significantly　higher　than　that　for　US　(0.574;　P　＜　0.001).　Compared　to　US　and　vascular　phase-CEUS,　postvascular　phase-CEUS　demonstrates　superior　sensitivity　(P　=　0.022,　and　＜　0.001,　respectively)　and　accuracy　(P　＜　0.001,　all)　for　diagnosing　LNs,　irrespective　of　LN　size.　ConclusionsPostvascular　phase-CEUS　exhibited　excellent　diagnostic　performance　in　identifying　suspected　small　LNs　in　cancer　patients.　Hyper-　or　isoenhancing　small　LNs　in　the　postvascular　phase　of　CEUS　were　unlikely　to　be　malignant,　possibly　obviating　biopsy.