Lamalunga Cave (Altamura, Southern Italy) is renowned for the discovery in 1993 of an excellently preserved Neanderthal skeleton. Given the importance of the findings and the potential use of Lamalunga speleothems for paleoclimate reconstructions, a detailed monitoring program was undertaken to investigate the connections between microclimate parameters and speleothem growth. The cave air temperature is characterized by annual sinusoidal cycles with increasing phase shift and decreasing thermal amplitude from ± 2.1°C to ± 0.04°C as a function of increasing rock overburden, and daily to sub-daily cycles induced by surface air pressure (SAP) variations characterized by strong 24-hour and 12-hour solar harmonic frequencies, with thermal amplitude decreasing from 0.0054°C to 0.0021°C in the deeper parts of the cave. The ventilation regime is mainly controlled by SAP fluctuations. Fast SAP rises can trigger “emptying events” during which most of the cave air is replaced and the CO2 concentration falls towards near-atmospheric values. The steady and gentle ventilation created by SAP fluctuations also influences the growth and morphology of calcite coralloids, with larger popcorn assemblages concentrated in the northern galleries and delicate branching morphologies prevailing along the South Gallery where stable temperature and relative humidity conditions occur. The study is a seminal example of how high-precision measurements of cave air temperature can provide a wealth of information on cave ventilation and thermal regime and provide valuable support for robust paleoclimate reconstruction from speleothems.