At the age of 24, R.E.G. Pichi Sermolli (1912–2005) travelled to Ethiopia as botanist on the Missione di Studio al Lago Tana, staying in Eritrea and Ethiopia from early January to late April 1937. The expedition was organized by the Centro Studi per l’Africa Orientale Italiana under the Reale Accademia d’Italia and resulted in 2649 collections of flowering plants. During the subsequent years of war, Pichi Sermolli had no time for his Ethiopian collections, but in 1947 he was able to identify them on visits to Geneva, Paris, Kew and London. Erbario Tropicale (FT) received the first set, and duplicates were distributed to other European herbaria. In 1951, Pichi Sermolli published a monograph of the collections, dealing with 520 species, describing 35 new taxa (28 of these were new species, and 11 were named after members of the expedition) and proposing 11 new combinations. The present paper reconstructs the outlines of Pichi Sermolli’s itinerary, maps almost all collecting localities, describes the complex history of the publications of the expedition and reviews the new taxa with indication of their taxonomic position in the Flora of Ethiopia and Eritrea. Eight of the 28 new species are still recognized, and they represent characteristic species of the Ethiopian highlands, particularly three species of Acacia. Pichi Sermolli’s experiences on the Lake Tana expedition resulted in a lifelong interest in Ethiopia, and the collections from the Lake Tana expedition mark a change in the history of the Erbario Tropicale, from an Italian colonial herbarium towards a tropical herbarium with international orientation.