The chemical investigation of the chloroform extract of Hypericum lanceolatumguided by 1H NMR, ESIMS, and TLC profiles led to the isolation of 11 new tricyclic acylphloroglucinol derivatives, named selancins A–I (1–9) and hyperselancins A and B (10and 11), along with the known compound 3-O-geranylemodin (12), which is described for a Hypericumspecies for the first time. Compounds 8and 9are the first examples of natural products with a 6-acyl-2,2-dimethylchroman-4-one core fused with a dimethylpyran unit. The new compounds 1–9are rare acylphloroglucinol derivatives with two fused dimethylpyran units. Compounds 10and 11are derivatives of polycyclic polyprenylated acylphloroglucinols related to hyperforin, the active component of St. John’s wort. Their structures were elucidated by UV, IR, extensive 1D and 2D NMR experiments, HRESIMS, and comparison with the literature data. The absolute configurations of 5, 8, 10, and 11were determined by comparing experimental and calculated electronic circular dichroism spectra. Compounds 1and 2were synthesized regioselectively in two steps. The cytotoxicity of the crude extract (88% growth inhibition at 50 μg/mL) and of compounds 1–6,8, 9, and 12(no significant growth inhibition up to a concentration of 10 mM) against colon (HT-29) and prostate (PC-3) cancer cell lines was determined. No anthelmintic activity was observed for the crude extract.