Calcium phosphate (CaP) stones account for about 15% of all urinary stones, with a marked female preponderance, and reflect a wide diversity of etiology. Variation of the relative prevalence of CaP urolithiasis over time is disputed, and relevance of CaP stone analysis for etiologic diagnosis is underestimated or even negated. Based on the analysis of more than 50,000 stones over the past three decades, we evaluated the changes in the relative proportion of CaP stones between 1980-1989 (period 1) and 2000-2009 (period 2). In addition, using morphologic examination combined with Fourier-transform infrared analysis, we assessed the associations between CaP stone analysis and etiopathogenic factors. Between periods 1 and 2, the overall proportion of struvite-free stones remained essentially unchanged (11.6 vs. 11.1%), with a decreasing proportion of carbapatite stones (10.6 vs. 8.4%, p < 0.001) and a rising proportion of brushite stones (0.8 vs. 2.2%, p < 0.001). Hypercalciuria was associated with 87% of brushite, and 60% of carbapatite stones. Urinary tract infection was associated with presence of minor amounts of struvite and/or with a carbonation rate of carbapatite > 15%. In CaP stones associated with primary hyperparathyroidism, the main component was carbapatite in 66.9% and brushite in 29.1% of cases. Distal renal tubular acidosis was always associated with carbapatite stones exhibiting a peculiar, virtually pathognomonic, morphology. In conclusion, comprehensive analysis of stones involving morphologic examination is of clinical relevance for improved etiologic evaluation of patients with CaP urolithiasis.