Serotonin (5‐hydroxytryptamine, HT), a neurotransmitter, and its main metabolite 5‐hydroxyindole‐3‐acetic acid (HIAA) are biomarkers for carcinoid tumors. They can be quantitatively detected by a new luminescent sensor based on a water stable lanthanide metal–organic framework (Ln‐MOF). This Ln‐MOF features a (3,4)‐connected topology containing 1D channels occupied by lattice water molecules. Luminescent studies reveal that high luminescence quenching efficiency occurs upon the addition of HT and HIAA. The Ln‐MOF also displays excellent sensitivity with fast response within 1 min, good reusability, and detection limits as low as 0.66 and 0.54 × 10−6m for HT and HIAA, respectively. In addition, the sensing function exhibits excellent selectivity even in the presence of other neurotransmitters and the main coexisting species in blood plasma and urine. Two novel water stable lanthanide‐functionalized metal–organic frameworks(Ln‐MOFs) with a 3D open framework are synthesized under hydrothermal conditions. Ln‐MOF 1 has the capability of sensing 5‐hydroxytryptamine (HT) and its major metabolite 5‐hydroxyindole‐3‐acetic acid (HIAA), which are effective discriminating biomarkers for carcinoid tumors. In addition, the sensing function can prevent from the interference of other coexisting species in blood plasma and urine.