In archaeology, the discovery of ancient medicines is very rare, as is knowledge of their chemical composition. In this paper we present results combining chemical, mineralogical, and botanical investigations on the well-preserved contents of a tin pyxis discovered onboard the Pozzino shipwreck (second century B.C.). The contents consist of six flat, gray, discoid tablets that represent direct evidence of an ancient medicinal preparation. The data revealed extraordinary information on the composition of the tablets and on their possible therapeutic use. Hydrozincite and smithsonite were by far the most abundant ingredients of the Pozzino tablets, along with starch, animal and plant lipids, and pine resin. The composition and the form of the Pozzino tablets seem to indicate that they were used for ophthalmic purposes: the Latin name collyrium (eyewash) comes from the Greek name κoλλύ ρα, which means "small round loaves." This study provided valuable information on ancient medical and pharmaceutical practices and on the development of pharmacology and medicine over the centuries. In addition, given the current focus on natural compounds, our data could lead to new investigations and research for therapeutic care. We present results combining chemical, mineralogical, and botanical investigations on the well-preserved contents of a tin pyxis. This pyxis was found onboard the Pozzino shipwreck discovered on the seabed of the Baratti Gulf (Fig. S1) at a depth of about 18 m near the remains of the Etruscan city of Populonia (Tuscany, Piombino, Italy) (4-6). The shipwreck was discovered in 1974 and the Soprintendenza per i Beni Archeologici della Toscana (archaeological authorities of Tuscany) undertook the first exploration in 1982 and archaeological excavation during [1989][1990]. The ship consisted of a small hull (15-18 m long and about 3 m wide) preserved only in the central part and inclined in the direction east-west, with the stern probably facing west. It was dated to the second half of the second century B.C. (probably 140-130 B.C.) on the basis of the archaeological findings. At that time, Populonia was of primary importance along the seatrade routes between the West and East, and this shipwreck bears witness to the republican trades across the Mediterranean Sea. Many interesting objects were found during the excavations, among them Sirian-Palestinian glass bowls, still stacked; WestSlope ware from Pergamon; some lagynoi; Rodian amphoras for wine transport; lamps of Ephesian origin; several tin and bronze vessels, such as one-handled jugs (one with a filter spout); oinochoai with trefoil mouths; ladles; and one inkwell, all of which came from the same geographical area. Such objects suggest that the ship, or at least a great part of its cargo, came from the east, probably the Greek coasts or islands. It is very likely that the ship was first equipped in the free harbor of the island of Delos (4, 5). The cargo also included medical equipment: numerous tin pyxides and 136 wooden vials were found close to an iro...